Expression of peroxisome proliferator-activated receptor α in rat fatty liver

AIM:To investigate the role of expression of peroxisome proliferator-activated receptor α(PPAR α) in pathogenesis of rat fatty liver.METHODS:The rats were treated with a low dose of carbon terachloride (CCl₄) and fed a high fat diet to produce fatty liver. We determined the concentrations of triglyceride (TG), total cholesterol (TC), free fatty acid (FFA) in liver and the alanine aminotransferase (ALT) activity, tumor necrosis factor-α (TNF-α), FFA in serum and the degree of hepatocytic steatosis. Total RNA of liver was extracted, and the expression of PPAR α were analyzed by semi-quantitative RT-PCR method.RESULTS:In model group, the hepatocytic PPAR α mRNA expression decreased to 0.41±0.28, compared to 1.41±0.29 in the control group (P＜0.01). The contents of TG, TC, FFA in model rat liver were (1.88±0.20) mmol·L^-1, (11.03±1.12) mmol·L^-1 and (1 260.38±151.27) μmol·L^-1, respectively, compared to (0.53±0.10) mmol·L^-1, (1.25±0.25) mmol·L^-1 and (334.30±27.09) μmol·L^-1 in the control group (P＜0.01). The activity of ALT, concentrations of TNF-α and FFA in serum were also increased remarkably in model group.CONCLUSION:Oxidation of fatty acid and utilization of lipids in liver are affected by reducing the expression of PPAR α, which result lipid accumulation in liver.     

Effect of curcumin derivative B06 Bob on synthesis of testosterone from type 2 diabetic rats

AIM: To investigate the effect of curcumin derivatives B06(B06) on the synthesis of testosterone from type 2 diabetic rats. METHODS: Male Sprague-Dawley rats were evenly divided into 5 groups randomly: normal control group (C group), high fat group (H group), high fat treatment group (HT group), diabetes mellitus group (D group) and diabetes treatment group (DT group). The rats in the later 4 groups were fed with high fat diet, after 4 weeks of high fat diet feeding, the rats from D group and DT group were injected with low dose of streptozotocin intraperitoneally to induce diabetes mellitus, while the rats in HT group and DT group were gavaged with B06 at the dose of 0.2 mg·kg^-1·d^-1 for 8 weeks. The blood glucose was detected by glucometer, blood insulin was assayed by ELISA and the insulin resistance index was calculated. The morphology of testes were observed by light and transmission electron microscopy. Serum testosterone and estradiol were measured by radioimmunoassay. The protein expression of steroidogenic acute regulatory protein (StAR) was detected by immunohistochemistry. The mRNA expression of StAR, cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17A1 (P450c17), cytochrome P450 aromatizing enzyme (P450arom), 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD was detected by RT-PCR. RESULTS: The levels of blood glucose and insulin resistance index were increased in H group and D group, and serum testosterone was decreased, all of which were reversed after the treatment of B06. Testicular seminiferous tubule was distorted, spermatogenic cells were dropped in H group and D group. In addition, leydig cells were found to have swelling mitochondria in H group and D group, endoplasmic reticulum was reduced, and there was karyopyknosis accompany with sparse chromatin, all of which were ameliorated by B06. The protein expression of StAR was decreased in D group. The mRNA expression of StAR and P450scc was decreased in H group and D group, all of which were increased in B06 treatment group. There was no significant difference in the mRNA expression of P450c17, P450arom, 3β-HSD and 17β-HSD. CONCLUSION: B06 may increase serum testosterone and relieve the damage of testes from type 2 diabetic rats. B06 improves metabolic disorder by up-regulating mRNA expression of StAR and P450scc.     

Alteration of serum free fatty acids during the carbon tetrachloride-induced fatty liver in rats

AIM: To investigate the alteration of serum free fatty acids in the carbon tetrachloride-induced fatty liver. METHODS: Drug-induced fatty liver rat models were built by injection 40% CCl₄. Serum free fatty acids were analyzed by gas chromatography. RESULTS: In the composition of serun free fatty acids, polyunsaturated fatty acids[oleic acid C18:1,(28.672±7.332/mg·L^-1 vs 41.373±2.180/mg·L^-1),linoleic acid C18:2(16.739±0.871/mg·L^-1 vs 24.959±5.325/mg·L^-1),arachidonic acid C20:4(6.105±2.656/mg·L^-1 vs 9.802±0.779/mg·L^-1),P<0 05], were decreased significantly, but saturated fatty acids [lauric acid C12：0(3.368±0.330/mg·L^-1 vs 2.742 0.351/mg·L^-1),myrist ic acid C14:0(27.136 3.158/mg·L^-1 vs 16.152±0.638/mg·L^-1),palmitic acid C16:0(51.731±9.561/mg·L^-1 vs 34.522±1.401/mg·L^-1),P<0 05] increased. CONCLUSION: Serum polyunsaturated fatty acids were decreased and saturated fatty acids increased in the drug-induced fatty liver.     

Effect of endoplasmic reticulum stress protein BiP on type 2 diabetic neuropathic pain in rats treated with curcumin

AIM: To investigate the effects of immunoglobulin heavy chain-binding protein (BiP),an endoplasmic reticulum stress protein, on mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), spinal dorsal horn and dorsal root ganglion (DRG) in type Ⅱ diabetic neuropathic pain rats treated with curcumin. METHODS: The rats were fed with a high-fat and high-fructose diet for 8 weeks to induce insulin resistance, and then were intraperitoneally injected with streptozotocin (STZ, 35 mg/kg). Eighty-one rats were selected into experimental design as their blood glucose ≥ 16.7 mmol/L 3 d after STZ injection and their MWT and TWL were decreased to 85% of the baseline values 14 d after STZ injection. The rats were divided into 3 groups (n=27 each): DNP group: type 2 diabetic neuropathic pain; DCur group: type 2 diabetic neuropathic pain and intraperitonal injection of curcumin at a dose of 100 mg·kg^-1·d^-1; DSC group: type 2 diabetic neuropathic pain and intraperitonal injection of corn oil at a dose of 4 mL/kg. Another 27 normal SD male rats fed with normal forage were adopted as control group (C group). MWT and TWL were measured at the time points of 3 d, 7 d and 14 d after curcumin injection. The lumbar segment 4~6 of the spinal cord and the corresponding DRG were removed at the same time. The expression of BiP was determined by immunohistochemical staining and Western blotting. RESULTS: Compared with C group, the rats in DNP group developed hyperglycemia and a decrease in MWT and TWL, as well as an increase in the activity of BiP in spinal dorsal horn and DRG (P<0.05). Compared with DNP group, the rats in DCur group at the time point of 7 d significantly attenuated mechanical allodynia and thermal hyperalgesia, and these effects were correlated with the inhibition of BiP hyper-activation at the time point of 14 d after treatment with curcumin (P<0.05). No significant difference of MWT, TWL and the expression of BiP between DNP group and SC group was observed. CONCLUSION: BiP participates in the pathogenesis of type Ⅱ diabetic neuropathic pain. Curcumin attenuates the MWT and TWL in type 2 diabetic neuropathic pain rats. The mechanism may be involved in the inhibition of BiP expression by curcumin.     

Intracerebroventricular injection of streptozotocin induces dysfunction of insulin signaling in brain and cognitive deficits in rats

AIM：To investigate the effect of insulin signaling on the development of Alzheimer disease (AD) and to explore its potential mechanisms. METHODS：The rats were treated with streptozotocin (STZ, 3 mg/kg) intracerebroventricularly (ICV) at the 1st day and the 3rd day of the experiment to induce dementia model. Twenty-one days after the injection of STZ at the 1st day, spatial learning and memory of the rats were determined by Morris water maze test. The expression levels of insulin-degrading enzyme (IDE), glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β (p-GSK-3β), tau and phosphorylated tau (p-tau) were measured by Western blotting. The levels of amyloid β-proteins (Aβ1-40 and Aβ1-42) in the brain of the rats were detected by the method of immunohistochemistry. The mRNA levels of insulin, insulin receptor, tau and IDE were measured by real-time RT-PCR. RESULTS：ICV-STZ deteriorated the abilities of spatial learning and memory of the rats and reduced the activity of IDE and the mRNA levels of insulin and insulin receptor. STZ treatment enhanced GSK-3β activity and tau phosphorylation. The levels of Aβ1-40 and Aβ1-42 in cerebral cortex were significantly increased in the rats treated with STZ. CONCLUSION：ICV-STZ results in AD-like behaviors and pathological changes via damaging the brain insulin signaling, indicating that insulin signaling may play important roles in the AD pathogenesis.     

Effect of erlotinib on renal injury in rats with STZ-induced diabetic nephropathy

AIM: To investigate the effect of epidermal growth factor receptor (EGFR) inhibitor erlotinib on kidney injury in diabetic nephropathy (DN) rat and the underlying mechanism. METHODS: The rat model of DN was induced by intraperitoneal injection of streptozotocin (STZ) at dose of 55 mg/kg. One week after STZ injection, the rats with blood glucose level exceeding 16.7 mmol/L were identified as diabetic. Diabetic rats were randomly divided into 2 groups:STZ group and STZ+erlotinib group. In addition, the normal rats were used as control group. The rats in STZ+erlotinib group were treated with erlotinib at 100 mg·kg^-1·d^-1 for 4 weeks(5th~8th week). The fasting blood glucose (FBG), serum creatinine (SCr) and 24 h urine protein were measured. The pathological changes of the kidney were observed by HE staining and Masson staining. The protein levels of EGFR, p-EGFR, transforming growth factor β1 (TGFβ1), Smad2/3, p-Smad2/3, collagen Ⅳ (ColⅣ) and fibronectin in the kidney tissues were determined by Western blot. The reactive oxygen species (ROS) level and malondialdehyde (MDA) content in the renal tissues were futher analyzed. RESULTS: Compared with control group, the levels of FBG, 24 h urine protein and Scr were significantly increased in STZ group (P<0.01). Compared with STZ group, the levels of FBG, 24 h urine protein and SCr in STZ+erlotinib group were markedly decreased (P<0.05). In additon, the glomerular structure was restored to normal, the proliferative degree of mesangial cells markedly attenuated, and the epithelial cells were in alignment in STZ+erlotinib group. Moreover, erlotinib significantly inhibited the protein levels of p-EGFR, TGFβ1, p-Smad2/3, ColⅣ and fibronectin in the kidney tissues of STZ rats. In addition, erlotinib also significantly inhibited the levels of ROS and MDA in the kidney tissues of STZ rats. CONCLUSION: Erlotinib ameliorates STZ-induced diabetic nephropathy possibly through inhibiting the activation of EGFR/TGFβ1-Smad2/3 signaling pathway in association with suppression of fibrosis and oxidative stress.     

Effects of different β-adrenergic receptors on cardiac systolic and diastolic functions in hypoxic stress rats

AIM:To explore the effects of different β-adrenergic receptors (β-AR) on the left and right ventricular systolic and diastolic functions in rats under acute hypoxic stress. METHODS:The healthy male SD rats were randomly divided into 4 groups (n=7):control group, non-selected β-AR blocker propranolol group, selected β₁-AR blocker atenolol group and selected β₂-AR blocker ICI 118,551 group, and then the rats were exposed to normoxia (20.9% O₂, 79.1% N₂) and hypoxia (15.0% O₂, 85.0% N₂) condition respectively at the altitude of 2 260 m (Xining, China). The heart rate (HR), the left ventricular systolic pressure (LVSP), the right ventricular systolic pressure (RVSP), and the maximum raise/decline rate of left and right ventricular pressure (±dp/dt_max) were monitored, and the arterial blood gas in normoxia and hypoxia condition were compared to explore the effect of β-AR on the left and right ventricular systolic and diastolic functions in acute hypoxic stress rats. RESULTS:Under normoxia condition, the LVSP, ±dp/dt_max of left ventricular were decreased in propranolol group, atenolol group and ICI 118,551 group, the RVSP and ±dp/dt_max of right ventricle were decreased in propranolol group and atenolol group (P<0.05). Under hypoxia condition, the PaO₂, LVSP, ±dp/dt_max of left ventricle were decreased in all groups compared with the normoxia group, and the ±dp/dt_max of right ventricle was increased in all groups (P<0.05), also the degree of index change in control group was more obvious than that in propranolol group and atenolol group. CONCLUSION:The activation of β₁-AR is an important compensatory regulation for heart function during hypoxic stress. However, the compensatory enhancement of right heart function under acute hypoxia condition which through tonogenic dilation is more significant for maintaining the normal circulating blood flow.     

Effects of curcumin analogue L6H4 on myocardial tissue of type 2 diabetic rats

AIM: To explore the effects of curcumin analogue L6H4 on the myocardial tissue of type 2 diabetic rats and its mechanism. METHODS: Male Sprague-Dawley rats were randomly divided into normal control (NC) group, high-fat (HF) group, high-fat treatment (FT) group, diabetes mellitus (DM) group and diabetes treatment (DT) group.The rats in the latter 4 groups were fed high-fat diet for 4 weeks, then the rats in DM groups and DT groups were intraperitoneally injected with streptozotocin (STZ) to induce type 2 diabetes, while the rats in FT group and DT group were given L6H4. The blood glucose and lipid levels were detected by biochemical method, and serum adiponectin (APN) levels were detected by ELISA. The serum insulin levels were measured by radioimmunoassay and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. The morphological changes of myocardium were observed by Masson staining and electron microscopy. The protein expression of adiponectin receptor 1 (AdipoR1) and transforming growth factor β1(TGF-β1) in myocardial tissue were determined by immunohistochemistry. The protein expression of adipoR1 was also detected by Western blot for verification. RESULTS: Compared with NC group, the blood glucose, lipids, insulin, HOMA-IR and TGF-β1 were increased in HF and DM group, but they were decreased after treated with L6H4. Compared with NC group, the concentration of serum APN were decreased and the expression of AdipoR1 in the myocardium were weakened in HF group and DM group, and they increased after treated with L6H4. The myocardial fibrosis was obvious in HF group and DM group, the mitochondria in cardiomyocytes expanded, and the cristae disordered, partial disappeared. These lesions were significantly reduced after L6H4 treatment. CONCLUSION: L6H4 exerts a protective effect on the heart in type 2 diabetic rats. The increased concentration of serum APN, the enhanced expression of AdipoR1, and the expression of TGF-β1 inhibited by APN may be involved in the mechanism of protection.     

Effects of resveratrol on cardiac dysfunction and ASMase-ceramide pathway in type 2 diabetic rats

AIM:To investigate the effects of resveratrol (RSV) on cardiac dysfunction and acid sphingomyelinase (ASMase)-ceramide pathway in diabetic rats. METHODS:Type 2 diabetes mellitus (T2DM) model was established by a high-fat diet combined with STZ intraperitoneac injection (30 mg/kg). SD rats (n=20) were randomly divided into control group, T2DM group; T2DM+RSV group (diabetic rats were given resveratrol at 100 mg·kg·d^-1 by intragastric administration for the treatment) and RSV group (some of control rats were selected to give the same dose of RSV for drug control group). The M-mode Doppler ultrasonography was performed to observe the changes of cardiac function and structure in the rats. The levels of serum glucose, lipid and superoxide dismutase (SOD) activity, malondialdehyde (MDA) content in heart tissues were measured. Oil red O staining and Sirius red staining were performed to observe lipid accumulation and cardiac fibrosis in heart tissues. The cardiac ceramide concentration in diabetic rats was analyzed by high-performance liquid chromatography. The protein expression of ASMase and peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) in the hearts was determined by Western blot. RESULTS:Compared with the control group, the levels of fasting blood glucose, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated in T2DM group. The values of ±dp/dt_max, fractional shortening and ejection fraction were declined, and the left ventricle internal dimension at end-systole (LVIDs) and left ventricle internal at end-diastole (LVIDd) were increased. Furthermore, increased MDA content and more lipid accumulation were also observed in diabetic hearts, while the SOD activity, ATP content and PGC-1α expression were reduced in diabetic hearts. However, all these parameters were reversed by addition of RSV, concomitant with decreased ASMase expression and ceramide content. CONCLUSION:RSV dramatically alleviates diabetes-induced cardiac dysfunction and cardiac fibrosis, which may attribute to inhibition of ASMase-ceramide activation.     

Effect of insulin combined with selenium on myocardial remodeling in diabetic rats

AIM: To investigate the effects of insulin combined with selenium on myocardial remodeling in streptozotocin (STZ)-induced diabetic rats.METHODS: The animal model of diabetic cardiomyopathy was induced by intraperitoneal injection of STZ (50 mg/kg) in rats. The level of blood glucose was estimated using One Touch SureStep blood glucose meter. Hemoglobin A1c level was detected by microcolumn assay. Triglyceride and total cholesterol were measured by enzymatic method. Collagen content in the myocardium was determined by Mallory staining. The expression of tumor necrosis factor α (TNF-α) in the serum and myocardium was observed by the methods of ELISA and immunohistochemistry, respectively.RESULTS: Compared with control group, the animals in model group showed metabolic disorders of glucose and lipid, and the cardiac function declined significantly (P<0.01).The myocardial cells showed disorder of distribution, filament breakage and collagen hyperplasia,and serum and myocardial TNF-α levels were significantly elevated.Insulin in combination with selenium significantly decreased the levels of blood glucose and lipid, and markedly inhibited the expression of TNF-α in the serum and myocardium than those in the rats administered with insulin alone (P<0.01).CONCLUSION: Combination of insulin and selenium significantly improves the structure and function of the heart by down-regulation of TNF-α.     

Metallothionein protects rat hepatic nuclear nucleoside triphosphatase from hydroxyl radical-induced suppression

AIM:Metallothioneins (MTs) are cysteine-rich metal-binding proteins that exert cytoprotection during metal exposure and oxidative stress. The present study was designed to investigate whether MT can directly protect NTPase on nuclear envelope from damage induced by hydroxyl radical.METHODS:Isolated hepatic nuclei from rat liver were exposed to Fe²⁺/H₂O₂ with or without MT, and the NTPase activity on nuclei was assayed using ATP and GTP as substrate, respectively.RESULTS:Incubation of rat hepatic nuclei with the Fe²⁺/H₂O₂ (in μmol·L^-1/μmol·L^-1 : 0.1/0.5, 0.5/2.5, 1/5, 5/25) resulted in a concentration-dependent decrease in nuclear NTPase activities (P＜0.01). Incubation of hepatic nuclei with different concentrations of MT (10^-9-10^-4mol·L^-1)and Fe²⁺/H₂O₂ (1 μmol·L^-1/5 μmol·L^-1) for 10 min, nuclear NTPase activities were increased in a MT concentration-dependent fashion as compared with that of incubation with Fe²⁺/H₂O₂(1 μmol·L^-1/5 μmol·L^-1) alone. When MT was at 10^-4 mol·L^-1, TNPase activities reversed to (102±10) nmol·mg^-1 protein·min^-1(for ATP as substrated) and (131±12) μmol·g^-1 protein·min^-1(for GTP as substrate), which had no significant defferences from that of the controls (112±8 and 142±10 μmol·g^-1 protein·min^-1, respectively) (P＞0.05). In addition, incubation of hepatic nuclei with only MT had no effect on nuclear NTPase activity. CONCLUSION:These data demonstrate that hydroxyl radical generated from Fe²⁺/H₂O₂ might attack nuclear NTPase. MT antagonistically reduces toxicity of Fe²⁺/H₂O₂ system to the NTPase.     

Renoprotective effect of L-carnitine on streptozotocin-induced diabetic nephropathy in rats

AIM: To investigate whether L-carnitine (LC) treatment confers renoprotection in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN). METHODS: Diabetic animal model was established by intraperitoneal injection of STZ (65 mg/kg) in Sprague-Dawley rats. Diabetic rats were treated with LC (50 mg·kg^-1·d^-1 or 200 mg·kg^-1·d^-1 intravenously) daily for 12 weeks. The effects of LC on STZ-induced DN were evaluated by assessing renal function, urinary protein excretion, histopathological changes, macrophage infiltration, the expression of proinflammatory and prosclerotic cytokines, and the expression of nuclear factor-κB (NF-κB) and apoptosis-related gene. RESULTS: LC administration significantly decreased glomerulosclerosis, preserved the number of podocytes, and reduced macrophage infiltration. These changes were accompanied by improvements in urinary protein excretion and renal dysfunction. LC treatment suppressed the expression of proinflammatory and prosclerotic cytokines, and these changes were paralleled by significant attenuation of NF-κB and apoptosis-related gene expression. CONCLUSION: LC has a renoprotective effect against STZ-induced DN in rats.     

IL-1β promotes differentiation of naïve T cells into Th22 cells and its expression in non-small cell lung cancer

AIM:To investigate the mechanism of interleukin-1β (IL-1β) promoting the transformation of naïve T cells into Th22 cells and the correlation of its peripheral blood expression in non-small cell lung cancer patients. METHODS:CD4⁺ naïve T cell magnetic bead sorting kit was used to isolate the peripheral blood mononuclear T cells from healthy people. Transforming growth factor-β (TGF-β) and IL-2 were added to promote differentiation and proliferation. IL-1β was used to induce differentiation into Th22 cells. The proportion of CD4⁺ IL-22⁺ T cells was analyzed by flow cytometry, and the expression of IL-22 was detected by ELISA. We selected 60 cases of non-small cell lung cancer patients in our hospital, including 18 in I phase, 20 in Ⅱ phase, 13 in Ⅲ phase and 9 in IV phase, as well as 25 healthy persons. The proportion of Th22 (CD4⁺ IL-22⁺) cells in peripheral blood was detected by flow cytometry, and the serum levels of IL-1β and IL-22 were measured by ELISA. RESULTS:IL-1β induced the transformation of naïve T cells into Th22 cells and promoted the secretion of IL-22 (P<0.05). The proportion of Th22 cells and the IL-22 and IL-1β levels in peripheral blood of the patients with non-small cell lung cancer were higher than those in healthy subjects, and correlated with the clinical stage. CONCLUSION:IL-1β induces the differentiation of Th22 cells and the expression of IL-22. The levels of IL-1β and IL-22 are related to the progression of non-small cell lung cancer, which may be involved in immunosuppression and promote the occurrence of non-small cell lung cancer.     

PPARs signaling pathway is involved in diabetic hepatopathy in mice

AIM: To investigate the role of peroxisome proliferator-activated receptors (PPARs)-inflammation signaling pathways in diabetic hepatopathy. METHODS: Diabetic mouse model was established by feeding the mice with a high-energy diet for 4 weeks combined with intraperitoneal injection of streptozotocin (STZ; 40 mg·kg^-1·d^-1 for 5 d). The hepatopathy model was confirmed by histopathological observation and the indexes of liver function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), after another 4 weeks. Moreover, fasting blood glucose (FBG), and serum levels of total cholesterol (TC), triglyceride (TG) and insulin were measured, and the HOMA insulin resistance index (HOMA-IR) was calculated. The mRNA and protein expression levels of PPARs and inflammation-related factors were measured by qPCR and Western blot, respectively. RESULTS: After treatment with STZ for 7 d, the FBG of mice exceeded 11.1 mmol/L, suggesting that the diabetic model was established. After 4 weeks, the structural deformation of the hepatocytes (including hepatocytes containing abundant fat vacuoles, and inflammatory cell infiltration), and the increases in the serum levels of insulin, HOMA-IR, TC, TG, ALT, AST and ALP were observed (P<0.01), indicating the occurrence and progression of hepatopathy in diabetic mice. Meanwhile, compared with the control group, the mRNA and protein expression of PPARα, PPARβ and PPARγ decreased, but the expression of nuclear factor-κB (NF-κB), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) significantly increased in the diabetic hepatopathy mice (P<0.01). CONCLUSION: Down-regulation of PPARα, PPARβ and PPARγ and activation of NF-κB-COX-2/iNOS signaling pathways may be involved in the diabetic hepatopathy in mice induced by long-term high-energy diet feeding combined with intraperitoneal injection of STZ.     

Effects of irbesartan on expression of integrin-linked kinase and podocyte injury in rats with early diabetic nephropathy

AIM: To determine the influence of irbesartan (Irb) on the podocyte injury and of integrin-linked kinase (ILK) expression in early experimental diabetic nephropathy (DN).METHODS: The hyperglycemic DN rat model was induced by intraperitoneal injection of streptozotocin (STZ,35 mg/kg) in spontaneously hypertensive rats (SHR).The diabetic SHR were randomly divided into 2 groups: DN SHR (DN,n=8) and DN SHR treated with irbesartan (50 mg/kg per day by gavage for 8 weeks,DN+Irb,n=9).Non-diabetic normotensive Wistar-Kyoto rats (WKY,the animals of normal blood pressure have the same genetic background with SHR) were used as control (control,n=11).The biochemical parameters and pathological changes were analyzed.Moreover,the influence of irbesartan on the expression of ILK and podocyte injury in SHR with DN was examined.RESULTS: Compared with control,DN SHR were associated with hyperglycaemia,hypertension,hyperlipidaemia,insulin resistance and albuminuria,which were similar to those of human T2DN.In addition,these DN SHR showed expansion of mesangial matrix,loss of podocyte and podocyte injury.Importantly,the expression of ILK in DN SHR was upregulated as compared to control.Treatment with irbesartan significantly decreased this overexpression of ILK,along with a decrease in albuminuria,reduction of blood pressure,prevention of podocyte injury,inhibition of mesangial matrix expansion and restoration of podocyte numbers.CONCLUSION: ILK is involved in the podocyte injury in DN.Irbesartan downregulates the expression of ILK and decreases podocyte injury.     

Protective effect of curcumin on myocardium in diabetic rats

AIM: To study the effects of curcumin (Cur) on diabetic cardiomyopathy (DCM) in rats. METHODS: Male Wistar rats (n=75) were divided into control group and diabetes model group, in which the rats were fed with high-fat diet and then intraperitoneally injected with streptozotocin (STZ, 40 mg/kg). Fasting blood glucose was measured 72 h and 1 week after STZ injection. The diabetic rats were diagnosed when sustained fasting blood glucose levels ≥ 11.6 mmol/L. The diabetic rats were randomly divided into DCM group, DCM+Cur 100 mg/kg group and DCM+Cur 200 mg/kg group. After treatment for 16 weeks, glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) level were measured, and the level of cardiac troponin I (cTnI) in the serum was determined by enzyme-linked immunosorbent assay. The protein expression of protein kinase C (PKC) was detected by Western blotting. RESULTS: Curcumin significantly decreased the blood glucose level, increased the body weight, inhibited MDA content and up-regulated the GSH-Px activity in the diabetic rats. Furthermore, curcumin treatment inhibited the diabetes-induced protein expression of PKC. CONCLUSION: Curcumin may have a protective effect on diabetic cardiomyopathy by attenuating oxidative stress.     

Effect of astragalus polysaccharin on expression of nephrin and podocin in podocytes of early diabetic nephropathy rats

AIM: To observe the effects of astragalus polysaccharin (APS) on the expression of nephrin and podocin in podocytes of diabetic nephropathy (DN) rats.METHODS: The rat model of diabetes was induced by intraperitoneal injection of streptozotocin (STZ).The diabetic rats were randomly divided into 2 groups by the treatment without or with APS: STZ group (n=8) and STZ+APS group (n=8).In addition, 8 non-treated rats served as control.All the rats were treated with APS or normal saline orally by gavage for 8 weeks.The concentration of blood glucose was monitored on week 2, 5 and 8 after treatment.Eight weeks later, the body weight and renal index were measured.Total urine protein in 24 h, blood urea nitrogen (BUN) and serum creatinine (SCr) were detected by biochemical methods.The pathological changes of the kidneys were also observed under light microscope.The protein levels of nephrin and podocin in the kidney tissues were also determined by Western blotting.RESULTS: After APS intervention, the levels of renal index, blood glucose concentration, 24-hour total urine protein, BUN and SCr were significantly lower and body weight was higher than those in STZ group (P<0.05).The renal pathological status in APS group was significantly improved and the expression levels of nephrin and podocin also markedly increased (P<0.05).CONCLUSION: APS might protect kidney against STZ-induced injury via increasing the expression of nephrin and podocin in podocytes.