Relationship between HDL subclasses and TC/HDL-C,TG/HDL-C ratio

AIM: To study the relationship between HDL subclasses and TC/HDL-C, TG/HDL-C ratio in serum. METHODS: Apolipoprotein (apo) A-Ⅰ contents of serum HDL subclasses in 292 subjects were determined by two-dimensional gel electrophoresis associated with immunodection method. RESULTS: Compared with low TC/HDL-C ratio subgroup, apoA-Ⅰcontents of preβ1-HDL (P<0.01, in middle or high subgroup) and HDL3a (P<0.05, in high subgroup) were significantly higher, but those of HDL2b (P<0.01, in middle or high subgroup) and HDL2a (P<0.01, in high subgroup) were significantly lower. Compared with middle TC/HDL-C ratio subgroup, apoA-Ⅰ contents of preβ1-HDL, HDL3a were significantly higher (P<0.01, P<0.05), but those of HDL2a and HDL2b were significantly lower (P<0.01, P<0.01) in high subgroup. Compared with low TG/HDL-C ratio subgroup, apoA-Ⅰ contents of preβ1-HDL, HDL3a were significantly higher (P<0.01, P<0.05, in high subgroup), but those of HDL2a and HDL2b were significantly lower (P<0.01, in middle or high subgroup). Compared with middle TG/HDL-C ratio subgroup, apoA-Ⅰ contents of preβ1-HDL, HDL3a were significantly higher (P<0.01, P<0.05), but those of HDL2a and HDL2b were significantly lower (P<0.01). In addition, TC, TG, TC/HDL-C ratio and TG/HDL-C ratio showed a positive correlation with apoA-Ⅰ contents of small-sized preβ1-HDL and a negative correlation with those of large-sized HDL2b, but it was reversed for HDL-C. CONCLUSION: When TC/HDL-C>5 or TG/HDL-C>2.2 in serum, the particle size of HDL shifted towards smaller sizes, which indicates that reverse cholesterol transport might be weakened and HDL maturation might be abnormal.     

Influences of apolipoprotein CII concentrations on high-density lipoprotein subclass distribution

AIM: To investigate the influence of serum apolipoprotein (apo) CII concentrations on the distribution of serum high-density lipoprotein (HDL) subclasses. METHODS: Serum HDL subclasses in 247 subjects were determined by two dimensional gel electrophoresis-immunodetection. RESULTS: With the increase in serum apolipoprotein CII levels, age, BMI, the contents of TG, TC, apoB100, apoCII, apoCIII, apoE, preβ1-HDL, preβ2-HDL, HDL3b and HDL3a increased significantly, but the contents of HDL-C, HDL2a and HDL2b decreased remarkably. The contents of preβ1-HDL increased with the rise in apoCII and apoA I levels, whereas the content of HDL2b increased with the rise in serum apoA I level in the same apoC II group, but decreased with the increase in serum apolipoprotein CII level in the same apoA I group. With the increase in the ratio of apoCII/ apoCIII, the content of preβ1-HDL elevated, but the content of HDL2b decreased. The correlation analysis illustrated that the apoCII level was positively correlated with preβ1-HDL (r=0.186, P<0.01), but inversely correlated with HDL2b (r=-0.149, P<0.05). The apoA I level was positively associated with all HDL subclasses (r in the range of 0.349-0.587, P<0.01). In addition, the apoCIII level was positively correlated with preβ1-HDL (r=0.184, P<0.01) and preβ2-HDL (r=0.178, P<0.01), while the apoE level was positively correlated with HDL3a (r=0.040, P<0.05). The apoB100 level was inversely correlated with HDL2a (r=-0.102, P<0.05). CONCLUSION: The particles of HDL show a general shift towards smaller size with the increase in apoCII levels, indicating that the maturation of HDL is abnormal. Whereas the contents of apoA I level correct the effect of apoCII on the distribution profile of HDL subclasses. The ratio of apoCII/apoCIII might also been taken as one of the indexes reflecting the distribution profile of serum HDL subclasses.     

Subclasses of serum HDL in middle and old aged patients with hyperlipidemia in Chengdu City

AIM: To detect the change of composition and ratio of serum HDL subclasses and explore the relationship between these changes and the plasma lipid level in patients with hyperlipidemia. METHODS: The components of subclasses of serum HDL in 172 middle and old aged patients with hyperlipidemia and 115 healthy middle and old aged were determined by dimensional gel electrophoresis associated with immuno-blotting method. RESULTS: Compared to the healthy controls, the contents of pre β1-HDL，　HDL3b and HDL3a were significantly higher (P＜0.05 or P＜0.01), while that of HDL2b was significantly lower (P＜0.01) in middle and old aged patients with hyperlipidemia. The content of pre β1-HDL increased with age in healthy controls, whereas the HDL2b decreased. The content of pre β1-HDL was significantly higher (P＜0.05), while the HDL2b (P＜0.05) was significantly lower in men than in women in patients with hyperlipidemia and the healthy controls. In middle and old aged patients with hyperlipidemia, the content of pre β1-HDL was positively correlated with the serum TG, TC, apoB100, apoCⅡ, apoCⅢ, apoE and TG/HDL-C (r=0.432; r=0.243; r=0.341; r=0.259; r=0.335; r=0.308 and r=0.453, P＜0.05 or P＜0.01), while it was negatively correlated with HDL-C (r=－0.167, P＜0.05). The content of HDL2b was negatively correlated with TG, TC, apoCⅡ, apoCⅢ and TG/HDL-C (r=－0.296; r=－0.156; r=－0.182; r=－0.216; r=－0.203 and r=－0.313, P＜0.05 or P＜0.01), while it was positively correlated with HDL-C (r=0.124, P＜0.05). CONCLUSIONS: The particle of HDL in the middle and old aged patients with hyperlipidemia showed a general shift towards smaller size, which indicated that the reverse cholesterol transport might be weakened. Men had smaller HDL particle size than women.     

Relationship between subclasses of serum HDL and LPL gene HindⅢ polymorphism in hyperlipidemia

AIM: To investigate lipoprotein lipase gene HindⅢ polymorphism and its relationship with serum lipids and apolipoprotein, serum HDL subclasses in patients with hyperlipoidemia. METHODS: Lipoprotein lipase gene HindⅢ polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 152 hyperlipoidemia patients and 128 healthy subjects were determined by two-dimensional gel electrophoresis conjunction with immunodetection method. RESULTS: H+H+ genotype and allele H+ in hyperlipoidemia and control groups were both the highest. In hyperlipidemia group, H+H+ genotypes tended to be higher than that in control group, while H+H- and H-H- genotypes were significantly lower (P<0.05). In hyperlipidemia group allele H+ carriers' frequency tended to be higher than that in control group (P<0.05). In hyperlipoidemia group, the genotype of H+H+ showed higher serum TG, apoB100 levels, TG/HDL-C ratio, preβ1-HDL, HDL3b and lower HDL2a, HDL2b compared with H-H- (P<0.05). In control group, the genotype of H+H+ had higher serum TG，HDL3c and lower HDL2a compared with H-H- (P<0.05). CONCLUSION: The HindⅢ polymorphism at intron 8 of LPL gene is associated with the general shift toward smaller size of HDL particle size in hyperlipoidemia, and the change of HDL subclasses distribution profile may be closely related to the pathogenesis of atherosclerosis in Chinese patients with hyperlipoidemia.     

Relationship of subclasses of serum HDL and Apo A-Ⅰ gene polymorphism in hyperlipidemia

AIM: To investigate apolipoprotein A-Ⅰ gene (Apo A-Ⅰ) polymorphism and its relationship with serum HDL subclasses in patients with hyperlipidemia (HL). METHODS: Apo A-Ⅰ genotype was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 118 patients with hyperlipidemia and 109 healthy subjects were determined by two-dimensional gel electrophoresis conjunction with immunodetection method. RESULTS: Both in HL group and the control group, G/G and C/C genotypes were the most frequent at －78 bp and ＋83 bp of Apo A-Ⅰ gene, respectively. The frequency of rare A allele at －78 bp in HL group was significantly higher than that in control group. In HL group, subjects with G/A mutation had higher serum levels of TG, Apo C-Ⅲ, pre β1-HDL and HDL3a, and lower levels of HDL2a and HDL2b compared to the subjects with G/G genotype. CONCLUSION: The G/A transition in the －78 bp position of the Apo A-Ⅰ gene promoter in patients with hyperlipidemia is associated with HDL subclasses. There is a general shift toward smaller sized HDL, which, in turn, indicates that HDL maturation might be abnormal.     

Relationship between HDL subclass distribution and plasma glucose and lipid levels in patients with metabolic syndrome

AIM: To investigate high-density lipoprotein(HDL) subclass distribution and to analyze the relationship between HDL subclasses with plasma glucose and lipids in metabolic syndrome(MS). METHODS: Apolipoprotein A-I(apoA-I) contents of plasma HDL subclasses were determined by two-dimensional gel electrophoresis associated with immunodetection. The concentrations of lipids and apolipoproteins in the plasma were measured by an automated biochemical analyzer. RESULTS: Compared with the controls, the levels of fasting plasma glucose(FPG), total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), LDL-C/high-density lipoprotein cholesterol(HDL-C), apolipoprotein B₁₀₀(apoB₁₀₀), apoB₁₀₀/apoA-I, systolic blood pressure(SBP), body mass index(BMI) and HDL_3b were increased in the MS patients(P<0.05). Meanwhile, HDL-C, apoA-I and preβ₂-HDL, HDL_2a and HDL_2b were decreased in the MS patients(P<0.01). With the increase in the plasma glucose level, the contents of HDL_2a and HDL_2b were decreased in the MS patients(P<0.05), while preβ₁-HDL was increased(P<0.05). With the decrease in the HDL-C level, the content of HDL_2b was decreased in the MS patients(P<0.01), while preβ₁-HDL was increased(P<0.01). With the increase in the TG level and the decrease in the HDL-C level, the content of HDL_2b had a decreasing trend and the content of small-particle preβ₁-HDL had an increasing trend, indicating that HDL maturation metabolism was disrupted. The correlation analysis showed that FPG was negatively correlated with the levels of HDL_2a and HDL_2b, HDL-C was negatively correlated with the level of preβ₁-HDL and positively correlated with the level of HDL_2b, and TG was positively correlated with the levels of preβ₁-HDL and HDL_3b. CONCLUSION: With the increases in the plasma glucose and TG, and the decrease in HDL-C in the MS patients, HDL particles have minifying tendency, and the maturation metabolism of HDL particles is disrupted.     

Influence of obesity on first-phase insulin secretion in individuals with different glucose tolerance

AIM: To explore the influence of obesity on the first-phase insulin secretion in the individuals with different glucose tolerance. METHODS: Thirty-eight subjects with normal glucose tolerance without family history of diabetes (normal control,NC), 32 subjects with normal glucose tolerance (NGT) who were the first-degree relatives of type 2 diabetic patients, 67 patients with impaired glucose regulation (IGR) and 35 newly-diagnosed type 2 diabetic patients (T2DM) were enrolled in the study. The patients in the 4 groups were further divided into 2 subgroups: overweight/obesity and normal weight subgroups. All subjects received oral glucose-insulin release test (OG-IRT) and intravenous glucose tolerance test (IVGTT). Acute insulin response at 3~5 min (AIR3-5) was used to reflect first-phase insulin secretion,and insulin sensitivity index (ISI) was used to reflect insulin sensitivity. The influence of obesity on the islet β-cell function and insulin sensitivity in the individuals with different glucose tolerance was observed. RESULTS: The level of AIR3-5 in NC overweight/obesity subgroup was significantly higher than that in normal weight subgroup (P<0.05), while there was no significant difference between other subgroups (P>0.05). No significant difference in the level of ISI between the patients of IGR in overweight/obesity subgroup and normal weight subgroup was observed, while in the other 3 overweight/obesity subgroups, ISI was lower than that in normal weight subgroups (P<0.05). ISI was negatively correlated with body mass index and waist circumference in all groups (P<0.05). ISI was also positively correlated with AIR3-5 in NC group and negatively correlated in the other 3 groups (P<0.05). CONCLUSION: The impact of obesity on insulin secretion is not the same in the subjects with different glucose tolerance. With the aggravation of insulin resistance, the first-phase insulin secretion in the subjects with normal glucose tolerance without family history of diabetes increases for compensation, while that in the normal glucose tolerance subjects who are the first-degree relatives of type 2 diabetic patients, the patients with impaired glucose regulation and the type 2 diabetic patients could not increase for compensation.     

Mast cells change cellular cholesterol content and inhibit cholesterol efflux from THP-1 macrophage-derived foam cells

AIM:Mast cells (MC) are present in the arterial intima,the site of atherogenesis. The present studies explore the effect of MC on cholesterol content,distribution and efflux in THP-1 macrophage-derived foam cells (THP-1FCs）. METHODS:THP-1FCs were incubated with high-density lipoproteins 3 (HDL₃) in the absence or presence of mast cell granules (MCGs) harvested from compound 48/80-stimulated rat peritoneal MC. The intracellular cholesterol level,cholesterol effluxing capacity,ATP-binding cassette transporter A1(ABCA1) mRNA and HDL₃ treated with MCGs were detected to characterize the role of MC on intracellular cholesterol. RESULTS:MCGs had high levels of cellular total cholesterol(TC),free cholesterol(FC) but not esterifed cholesterol(EC) compared to control group where the TC concentrations ranged from 527.3 mg/g to 917.9 mg/g cellular protein with EC accounting for 7.6% of the cholesterol. Cholesterol efflux was 14% less in MCGs group compared to control group. ABCA1 mRNA expression in MCG-treated THP-1FCs remained unchanged in 20 hours. In contrast,treatment of HDL₃ with MCGs resulted in rapid degradation of the main HDL₃ apoliproteins,apoA-Ⅰ. SDS-PAGE revealed that a minor polypeptide band with about 26 kD molecular mass appeared below the apoA-Ⅰband. Densitometric analysis of the gel demonstrated that ≈ 28% of apoA-Ⅰhad been degraded by the MCGs. CONCLUSION:These results indicate that MC decreases cholesterol efflux,increases cellular accumulation in TC and FC by depleting HDL₃ and apoA-Ⅰ,but not by inhibiting ABCA1 mRNA expression.     

The relationship between high density lipoprotein subclasses and apoE gene polymorphism in obese subjects

AIM: The purpose of this study is to elucidate the relationship between apolipoprotein (apo) E polymorphism and plasma lipid profiles and HDL subclasses in obesity. METHODS: apoE genotype was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 93 obese subjects and 96 nonobese subjects were determined by two-dimensional gel electrophoresis conjunction with immunodetection method. RESULTS: apoE3/3 genotypes and allele ε3 frequency in obese group and the control group were both the highest, but no significant difference. In obese group, the genotype of apoE2 had higher serum apoE/aopCⅢ, HDL2a and lower apoB100, apoCⅢ, HDL3c levels compared with the genotype of apoE3 (P<0.05). In control group, the genotype of apoE2 had higher serum TC and apoE levels, but lower HDL3b level compared with the genotype of apoE3 (P<0.05). CONCLUSION: Polymorphism of the ApoE gene is associated with the distribution of HDL particles in obesity. Allele of ε2 carrier may slow the tendency of HDL particals shifted towards smaller sizes.     

Association between apolipoprotein E polymorphism and lipid metabolism in patients with cerebral infarction

AIM:To study the relationship between ApoE polymorphism and lipid metabolism of patients with cerebral infarction. METHODS:ApoE phenotype was determined in 110 patients with cerebral infarction and 60 normal controls by isoelectric focusing and immunoblotting. The TC, TG and HDL-C levels in serum of these subjects were measured with enzymes methods, ApoA I and ApoB levels with rocket immunoelectrophoresis methods, ApoE and Lp(a) levels with ELISA methods. RESULTS:The differences of the ApoE polymorphism distribution and ApoE allele frequencies (P＜0.05) occurred between two groups. The frequence of ApoE ε4 allele in patients with cerebral infarction was significantly higher than those in the normal controls (P＜0.05). However, ApoE 3/3 phenotypes was significantly lower (P＜0.05). Comparison of values of serum lipid with various ApoE phenotyoe among patients with cerebral infarction revealed that there was correlation between ApoE polymorphism and TC(P＜0.05), TG(P＜0.05), HDL-C(P＜0.05), LDL-C(P＜0.05), ApoA I(P＜0.05), ApoB(P＜0.05), ApoE(P＜0.05)and Lp(a)(P＜0.05). Patients carrying ε4 were associated with increased TC, LDL-C, ApoB and Lp(a), while those with ε2 were assiociated with decreased TC, LDL-C, and ApoB. Patients carrying ε2 were associated with increased TG, HDL-C, ApoAⅠ, and ApoE.CONCLUSIONS:ApoEε4 allele was associated with the development of cerebral infarction. ApoE polyphorphism affects lipid metabolism of cerebral infarction patients.     

Effects of Shan He Jian Fei Granule on the expression of leptin,adiponectin and resistin in obese rats induced by high-fat feeding

AIM: To study the effects of Shan He Jian Fei Granule (SHJFG), a Chinese medicine, on weight-reduction and fat-decrease in adiposity rats, and to observe the changes of leptin, adiponectin and resistin. METHODS: After the models were prepared successfully, the rats were randomly divided into four groups: normal group, low dosage, middle dosage, high dosage and obesity control group. After 8 weeks interference with SHJFG, the weight and the naso-anal length of each rat was measured and Lees index were calculated. The levels of TG, TC, LDL, HDL and leptin in serum were carefully determined. The gene expressions of adiponectin and resistin in adipose tissues of rats were determined by RT-PCR. RESULTS: Compared to high-fat diet group, the body weights, the Lees indexes, the weight of fat tissues and levels of TG, TC, LDL and leptin in SHJFG groups significantly decreased (P<0.05). Adiponectin mRNA expression in SHJFG group significantly increased (P<0.05), and the resistin mRNA expression also significantly increased. CONCLUSION: SHJFG significantly decreases the body weight and the serum levels of TG, TC and LDL in obese rats. The effects of SHJFG in raising the mRNA expressions of adiponectin and resistin in fat tissues may be one of the main role that results in lowering body weight in obese rats.     

GLP-1 down-regulates mRNA expression of SOCS-3 and SREBP-1c in rats with nonalcoholic fatty liver disease

AIM: To investigate the effects of glucagon-like peptide-1(GLP-1) on mRNA expression of SOCS-3 and SREBP-1c in the rats with nonalcoholic fatty liver disease. METHODS: Male SD rats were randomly divided into normal control(NC) group, high fat(HF) group and HF+liraglutide(Lira) group. The rats in HF group and HF+Lira group were given high-fat diet for 16 weeks. After 12 weeks of high-fat diet feeding in HF+Lira group, Lira(600 μg·kg^-1·d^-1) was intraperitoneally injected for 4 weeks. At the end of the 16th week, the rats were killed. The pathological changes of the liver were observed under optical microscope. The serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglyceride(TG) and total cholesterol(TC) were detected by automatic biochemical analyzer. TG contents of liver were measured by GPO-PAP method. The fasting insulin(FINS) was determined by ELISA, and insulin resistance index was assessed by homeostasis mode assessment(HOMA-IR). The mRNA expression of SOCS-3 and SREBP-1c in the liver tissues was detected by RT-qPCR. RESULTS: Compared with NC group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF group were obviously increased(P<0.01). Compared with HF group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF+Lira group were all obviously decreased(P<0.05 or P<0.01). The mRNA expression of SOCS-3 and SREBP-1c in HF group was significantly higher than that in NC group(P<0.01). The mRNA expression of SOCSV3 and SREBP-1c in HF+Lira group was significantly decreased as compared with HF group(P<0.05). CONCLUSION: Liraglutide may improve the IR and reduce TG of liver through decreasing the mRNA expression of SOCS-3 and SREBP-1c, so as to play a therapeutic role in nonalcoholic fatty liver disease.     

Effect of micronised fenofibrate on lipotoxicity and insulin sensitivity in spontaneously hypertensive rats treated with high-fat diet

AIM: To observe the effect of micronised fenofibrate (lipanthyl) on lipotoxicity and insulin sensitivity (IS) in spontaneously hypertensive rats (SHR) with high-fat diet.METHODS: Twenty-seven SHR were randomly divided into three groups: normal chow group (n=9), high-fat diet group (n=9) and micronised fenofibrate treatment group (n=9). Micronised fenofibrate 100 mg·kg-1·d-1 was given orally to SHR, which diet on high-fat diet for three months. Intramuscular lipids were observed and lipids accumulation index (LAI) was calculated. Nonesterified fatty acid, glucose and insulin were determined in all rats.RESULTS: (1) Compared to SHR in normal chow diet group, body weight and the level of serum TG and TC increased significantly and the level of HDL-C decreased significantly in SHR fed with high-fat diet (P<0.05). Micronised fenofibrate significantly decreased systolic blood pressure, body weight, the level of serum TG and TC, increased the level HDL-C (P<0.05). (2) Fasted blood glucose, free fatty acid (FFA), GLU-AUC obviously increased in high-fat diet group compared with normal chow diet group. Insulin sensitivity index (ISI) in high-fat diet group was much lower than that in normal chow diet group (0.0038±0.0007 vs 0.0053±0.0013, P<0.05). No difference was found between fenofibrate-treated group and normal chow diet group. (3) There were more lipid drops in intramuscular cells of SHR treated with high-fat diet than those in fenofibrate-treated group and normal chow diet group (LAI: 6.42±0.59 vs 3.32±0.77 and 1.98±0.97, P<0.05). After covariance analysis, the results above-mentioned also made sense (F=10.46, P<0.05). (4) Inverse association was found between LAI and ISI (r=-0.58, P<0.05). Positive correlations were found between LAI and TG, FFA, body weight.CONCLUSION: In addition to regulating lipid, micronised fenofibrate may reduce BP, body weight, FFA, lipid accumulation in intramuscular cells and improve insulin sensitivity of SHR treated with high-fat diet.     

Effects of intranasal Escherichia coli on glucolipid metabolism in high-fat diet-induced obese mice

AIM: To study whether the pulmonary infection of Escherichia coli (E. coli) interferes the glucolipid metabolism in high-fat diet-induced obese mice. METHODS: High-fat diet-induced obese mice (n=48) and normal chow-fed control mice (n=48) were intranasally infused with 40 μL fluid containing 4×10⁹ CFUs E. coli. The serum, periepididymal adipose tissue and liver were obtained at 0 d, 1 d, 2 d, 3 d and 4 d after infection. The body mass, periepididymal adipose tissue and liver were weighed, and the levels of fasting blood glucose (FBG), fasting blood insulin (FINS), free fatty acid (FFA) and very-low-density lipoprotein (VLDL) were measured by ELISA. The serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and hepatic TG contents were detected, and the hepatic steatosis was observed under microscope with oil red O staining. RESULTS: Compared with day 0, the body mass, fat mass and fat index were decreased significantly from day 1 to day 4 after infection (P<0.05). The levels of FBG, FINS and HOMA-IR were apparently raised from day 2 to day 4 after infection (P<0.05). The contents of serum FFA, TG and VLDL were increased markedly from day 1 to day 4 after infection (P<0.05). However, the concentrations of serum TC, LDL-C and HDL-C were decreased obviously from day 1 to day 3 (P<0.05). The liver mass, liver index and TG content were significantly increased from day 1 to day 4 (P<0.05). Consistently, the lipid droplet accumulation in the liver cells was increased obviously at day 2 and day 4 after infection. Compared with control group, except the levels of serum TC, LDL-C and HDL-C in obese group substantially decreased, the other indexes were increased by different degrees during the whole experiment period (P<0.05). CONCLUSION: Pulmonary infection of Escherichia coli exacerbates the disorder of glucose and lipid metabolism in high-fat diet-induced obese mice, which contributes the development of insulin resistance and hepatic steatosis.     

The impact of scavenger receptor class A typeⅠ/Ⅱ on lipid metabolism in mice

AIM: To investigate the impact of scavenger receptor class A type Ⅰ/Ⅱ(SR-A Ⅰ/Ⅱ) on the lipid metabolism in SR-A Ⅰ/Ⅱ gene deficient mice. METHODS: A probe of 660 bp fragment of SR-A Ⅰ/Ⅱ cDNA digested with PstⅠ and XhoⅠ from plasmid 122 was used to identify whether SR-A Ⅰ/Ⅱ had been knocked out in the tail DNA of the mutant(SR-/-) and control(SR+/+) mice by the method of Southern-blot analysis. The serum levels of triglycerides(TG), cholesterol(CH), low density lipoprotein(LDL), high density lipoprotein(HDL), apolipoprotein(Apo) A and ApoB of the mice fed with normal food and higher lipid food respectively were tested by biochemical method. RESULTS: The serum levels of LDL and body weights of group with SR-A Ⅰ/Ⅱ gene knocked out were higher than that of control group(P<0.05). Although the disorders of serum levels of LDL and body weights deteriorated after high lipid diet in both groups, the disorders in group of SR-/- were worse than those in control group(P<0.01). CONCLUSION: The results demonstrated that SR-A Ⅰ/Ⅱ were involved in the regulation of lipid metabolism, and SR-A Ⅰ/Ⅱ deficiency is harmful for removing LDL from blood circulation.     

Relationship between the E-selectin and oxidative stress in patients with obese type 2 diabetes mellitus

AIM: To investigate the relationship between the levels of soluble E-selectin and oxidative stress in patients with obese type 2 diabetes mellitus.METHODS: The level of E-selectin, the contents of ox-LDL and malondialdehyde (MDA) and activities of superoxide dismutase (SOD) were measured in patients with obese and non-obese type 2 diabetes mellitus.RESULTS: The levels of E-selectin, ox-LDL and MDA were higher in patients with obese type 2 diabetes mellitus than those in control group (P<0.05), and the contents of HDL-C, HDL2-C and HDL3-C were significantly lower than those in control group (P<0.01).The activity of SOD in patients with obese type 2 diabetes mellitus was significantly lower than that in control group.The contents of E-selectin and MDA were more markedly elevated in patients with obese type 2 diabetes mellitus than those in patients with non-obese type 2 diabetes mellitus (P<0.01,P<0.05) and the activity of SOD was also significantly lower than that in patients with non-obese type 2 diabetes mellitus (P<0.01).There was significantly positive correlation between E-selectin and HbA1c, waist circumference, TC, ox-LDL, MDA (r=0.352, P<0.05;r=0.634, P<0.05;r=0.517, P<0.05;r=0.480, P<0.05;r=0.572, P<0.05), and negatively correlation between E-selectin and HDL3-C (r=-0.374, P<0.05).CONCLUSION: The plasma level of E-selectin is markedly elevated in patients with obese type 2 diabetes mellitus.E-selectin is possibly associated with oxidative stress.     

IL-1B-511 single nucleotide polymorphism and gastric atrophy in high prevalence regions of gastric cancer in China

AIM: To study the relationship between IL-1B-511 single nucleotide polymorphism,H.pylori infection,and gastric atrophy in high prevalent (Shanxi) region in China.METHODS: Five hundred healthy volunteers from Shanxi Province of China were recruited in this study,which were divided into five subgroups according to age,namely age 20-29,30-39,40-49,50-59 and >60 years,respectively.Genomic DNA was extracted from peripheral blood.IL-1B-511 single nucleotide polymorphism was analyzed by PCR-RFLP.Serum pepsinogen was used as a biomarker of gastric atrophy.Serum pepsinogen Ⅰ (PGⅠ),pepsinogen Ⅱ (PGⅡ) and anti-H.pylori IgG were determined by an ELISA assay.RESULTS: The mean serum PGⅠ concentration and ratio of PGⅠ /PGⅡ decreased gradually with increasing age,and were lower in subjects with IL-1B-511 T/T genotype and H.pylori infection than those without H.pylori infection in each subgroup,respectively (All P<0.05).Multiple linear regression showed that IL-1B-511 T/T genotype,age and Hp infection were significantly associated with gastric atrophy (P<0.05,P<0.05 and P<0.01,respectively).CONCLUSION: Gastric atrophy is closely correlated with IL-1B-511 T/T genotype,age,H.pylori infection in high prevalence region of gastric cancer in China.The risk of gastric atrophy is significantly increased for the IL-1B-511 T/T genotype with Hp infection.     

Effects of Taoren Honghua Jian on the hyperlipidemia without symptom

AIM: To examine the effect of traditional chinese medicine recipe, Taoren Honghua(semen persicae-flos carthami) decoction, on hyperlipidemia without symptom. METHODS: The plasma TC, TG, LDL, HDL, apolipoprotein(Apo) A, Apo Bof the patients with hyperlipidemia without symptom were measured using automatic analyzer (shimadiu CL-7200), the production of nitric oxide(NO) was detected by Greiss reaction, and SODactivity and MDAformation were examined using o-trihydroxy benzene and barbituric methotheds, respectively. RESULTS: After oral administration of Taoren Honghua decoction, the plasma levels of TC, TG, LDL, and MDAof the patients were markedly decreased, however, the plasma levels of ApoA, HDL, SODand NOwere significantly increased and almost no change was detected in the plasma level of Apo B. In control group, it was found that although the plasma level of TC, TG and LDL were decreased ( P<0.05 ) and ApoAas well as HDLwere increased, ApoB, SOD, MDA and NO production were all unchanged. CONCLUSION: The traditional chinese medicine recipe, Taoren Honghua decoction,has a significant therapeutic effect on patients with hyperlipidemia by removing blood stasis, promoting qi circulation and in turn reducing blood lipid level.     

Correlation between TAFI and blood fat and coagulation in the process of atherosclerosis

AIM: To investigate the relationship between the thrombin-activatable fibrinolysis inhibitor (TAFI) level in plasma and atherosclerosis, the TAFI level in plasma and blood fat and blood clotting index.METHODS: Totally 40 healthy male Wistar rats were randomly divided into 4 groups (n=10), control group, high lipid group, high lipid +vitamin D3 overload group, and high lipid +vitamin D3+endothelium injure group by treating the animals with normal diet, high lipid, high lipid+ vitamin D overload, and high lipid+vitamin D overload+endothelium injury, respectively, for inducing three stages of AS in rats. Then, the total cholesterol (TC), total triglyeride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), and prothrombin time (PT), activated partial thromboplasin time (APTT), fibrinogen (Fib), the activity of TAFI were measured.RESULTS: TC, TG, LDL-C, Fib and the activity level of TAFI in plasma in three model groups increased gradually compared with the control (P＜0.01). HDL-C, PT and APTT in plasma of three model groups decreased gradually compared with the control (P＜0.01 or P＜0.05). The activity of TAFI in plasma had positive correlation with TG, TC and Fib.CONCLUSION: The activity of TAFI increases in the progress of atherosclerosis. The activity of TAFI in plasma has a correlation with blood fat and coagulation, which indicates that TAFI might participate in the process of atherosclerosis, and TAFI is one of etiological factors of atherosclerosis.     

Oxymatrine ameliorates high fat-induced insulin resistance in ApoE-/- mice

ATM: To investigate the effect of oxymatrine (OXY) on high fat-induced insulin resistance in mice, and to investigate the mechanism. METHODS: ApoE^-/-mice with high-fat diet for 16 weeks were divided into insulin resistance group, and OXY groups at concentrations of 25, 50 and 100 mg/kg. C57BL/6J mice served as normal control group. The mice in OXY groups were gavaged with OXY for 8 weeks. Glucose tolerance test in the mice was performed. Fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), fatty acid (FFA) and fasting insulin (FINS) in the plasma were measured. The mRNA expression of insulin receptor (INSR), insulin receptor substrate-2 (IRS-2), glucose transporter 2 (GLUT2) in the liver tissues was examined by RT-qPCR. The protein levels of GLUT2, INSR, IRS-2, p-INSR, p-IRS-2, PI3K, p-PI3K, serine/threonine protein kinase (AKT) and p-AKT were examined by Western blot.RESULTS: OXY reduced the levels of FBG, TC, TG, FFA and FINS, and attenuated insulin resistance. Compared with insulin resistance group, the mRNA expression of INSR, IRS-2 and GLUT2 significantly increased in OXY groups (P<0.05). The protein levels of p-INSR/INSR, p-IRS-2/IRS-2, p-PI3K/PI3K, p-AKT/AKT and GLUT2 also increased in OXY groups (P<0.05).CONCLUSION: OXY ameliorates high fat-induced insulin resistance in mice via PI3K/AKT pathway.