Correlation of serum uric acid level with carotid plaques and arterial stiffness in patients with essential hypertension

AIM：To study the correlation of serum uric acid (UA) level with carotid plaques and arterial stiffness in the patients with essential hypertension (EH), and to explore the predictive value of serum UA for evaluating EH preclinically. METHODS：A total of 92 patients with EH and 30 healthy individuals were enrolled. The value of UA and other indicators were detected. B-mode ultrasound examination was performed to measure the common carotid artery intima-media thickness (IMT) and the sites of plaque in the internal carotid-artery, external carotid artery and carotid bifurcations. Carotid-femoral arterial pulse wave velocity (CFPWV) was assessed by Complior atherosclerosis measurement instrument. RESULTS：The serum level of UA in the patients with EH was higher than that in control group ［(361.51±83.81） μmol/L vs (317.03±62.22) μmol/L, P<0.05］. The mean value and abnormal rate of IMT between hypertension group and control group were significant difference ［(0.69±0.14) mm vs (0.60±0.12) mm, 42.39% vs 10.00%, P<0.05］. In 92 EH patients, 45 cases had carotid plaques. These 45 cases were divided into 3 groups according to the plaque severity, among which the serum UA level had statistically significant differences ［(285.25±78.41） μmol/L, （341.19±63.99） μmol/L and （401.33±88.49） μmol/L, P< 0.05］. Compared with rigid plaque group (n=34), the serum UA level in soft plaque group (n=11) was significantly higher ［(389.00±69.45) μmol/L vs （323.03±72.71） μmol/L, P<0.05］. A stepwise multiple linear regression analysis demonstrated that age (r=0.414), systolic blood pressure (r=0.224), pulse pressure (r=0.270) and uric acid (r=0.219) were predisposed factors for higher CFPWV (P<0.05). CONCLUSION：UA is one of the risk factors causing hypertension. Serum UA level may reflect the severity and stability of carotid plaques. The increased arterial stiffness is closely related to the increased serum UA level in EH.     

Complement activation in acute coronary syndromes

AIM: To evaluate complement activation in patients with all forms of acute coronary syndromes (ACS) and to examine the relationship between the degree of complement activation and myocardial injury.METHODS: The subjects were divided into 2 groups: 110 ACS patients (group ACS) and 18 healthy persons (group control).One hundred and ten patients with ACS were divided into 3 sub-group: 51 patients with ST-segment elevated myocardial infarction (STEMI),28 patients with non-ST-segment elevated myocardial infarction (NSTEMI) and 31 patients with unstable angina (UA).Complement 3 (C₃),complement 4 (C₄),troponin T (TnT) as well as creatine kinase MB (CK-MB) were evaluated.RESULTS: Plasma C₃ and C₄ peak levels were significantly higher in patients with STEMI ［(1 525±302)mg/L and (423±123) mg/L］ and NSTEMI ［(1 516±289)mg/L and (396±68) mg/L］ than those in patients with UA ［(1 275±172)mg/L and (356±91) mg/L］ and the control subjects ［(1 072±196)mg/L and (182±73) mg/L］ (P<0.01 for all).Also,C₃ and C₄ serum levels in patients with UA were significantly higher than those in control subjects (P<0.01 for all).At one-week follow-up,plasma levels of C₃ and C₄ were significantly different among various days in patients with ACS (P<0.01).Plasma C₃ and C₄ levels in ACS showed a relationship with peak creatine kinase MB (CK-MB) and troponin T (TnT) levels (P<0.01).CONCLUSION: Plasma C₃ and C₄ levels are elevated in ACS in present study.The relationship between C₃,C₄ levels and ACS suggests that the complement activation is related to necrosis within the myocardium.     

Effects of pentoxifylline on ventricular remodeling and cardiac function of dilated cardiomyopathy rats

AIM: To explore the effects of pentoxifylline (PTX) on ventricular remodeling and cardiac function in dilated cardiomyopathy (DCM) rats.METHODS: Lewis rats were randomly allocated to a myocin-induced dilated cardiomyopathy (DCM) group receiving saline (n=10), a DCM group receiving PTX (PTX group; 25 mg·kg^-1·d^-1, ip, for 30 days, n=10) or healthy control group (n=10). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 in the blood plasma were analyzed by ELISA. The extent of fibrosis was estimated using Massons staining and immunohistochemistry analyses. Cardiac structure and function were measured by echocardiography.RESULTS: PTX decreased plasma levels of TNF-α and IL-6, and increased IL-10 level in DCM animals compared with DCM group ［TNF-α: (7.21±0.24) μg/L vs (19.30±1.31) μg/L, P<0.01; IL-6: (119.60±36.58) ng/L vs (189.50±13.25) ng/L, P<0.05; IL-10: (41.26±3.27) μg/L vs (32.45±4.32) μg/L, P<0.05］. Collagen volume fraction (CVF), perivascular collagen area (PVCA) and collagen Ⅰ/Ⅲ ratio were lower in PTX group than those in DCM group ［CVF: (16.45±3.01)% vs (23.33±4.43)%, P<0.05; PVCA: 4.58±2.10 vs 13.74±4.29, P<0.05; Ⅰ/Ⅲ ratio: 2.84±0.67 vs 4.22±0.54, P<0.01］. Left ventricular end-diastolic dimension reduced ［(6.11±0.51) mm vs (6.46±0.28) mm, P<0.05］ and left ventricular ejection fraction elevated ［(77.29±5.20)% vs (62.73±10.11)%, P<0.01］ by PTX compared with DCM.CONCLUSION: PTX modulates plasma levels of inflammatory cytokines, delays the ventricle remodeling and improves the heart function in DCM rats.     

Effect of rosiglitazone on myocardial energy substrate utilization in type 2 diabetic rats

AIM: To study the effect of rosiglitazone (RSG) to improve insulin sensitivity on myocardial energy substrate utilization as well as the cardiac function in a rat model of type 2 diabetes mellitus. METHODS: Sprague-Dawley rats were conducted into three groups: chow-fed rats were fed with normal chow (12% of calories as fat); fat-fed/STZ rats were fed with high-fat diet (40% of calories as fat) for 4 weeks and then injected with streptozotocin 35 mg/kg intraperitoneal; fat-fed/STZ/RSG rats were fat-fed/STZ rats treated with rosiglitazone (3 mg·kg-1·d-1) for 2 weeks. A cannula connected to a passive transducer was inserted the heart for the measurement of the cardiac function including heart rate (HR), left ventricular end-diastolic pressure (EDP) and ±dp/dtmax. Then the isolated hearts were mounted onto a Langendorff perfusion apparatus to perfuse with Krebs-Henseleit buffer in the presence of 5 mmol/L glucose and 0.4 mmol/L ［3H］ labelled palmitate. Glucose uptake and ［3H2O］ collection were measured to evaluate the rate of carbohydrate and fatty acid oxidation. RESULTS: Compared with the chow-fed rats, fat-fed/STZ rats had a significantly depression of glucose uptake in the hearts ［(54.7±6.2 vs 69.0±5.7) μmol·g-1 dry weight, P<0.01］ after 30 min perfusion. The oxidation of glucose and palmitate were 18% and 82%, respectively. Paralleling the reduction was a change of EDP ［(14.3±1.8 vs 10.5±1.1) mmHg, P<0.05］ and -dp/dt ［(550±57 vs 650±42) mmHg/s, P<0.01］, indicating a impaired left ventricular diastolic function. In the hearts subjected to fat-fed/STZ group, rosiglitazone treated for 2 weeks resulted in a elevated level of glucose uptake ［(63.5±6.4 vs 54.7±6.2) μmol·g-1 dry weight, P<0.05］. A protective role of the ventricular function ［EDP decreased from （14.8±1.9） to （11.0±0.8） mmHg/s and -dp/dtmax increased from （558±60） to （629±51） mmHg/s, P<0.05］ were observed. CONCLUSIONS: Our study indicates that there is a depression of glucose oxidation and at increase in fatty acid oxidation in type 2 diabetic hearts. Elevation of insulin sensitivity using rosiglitazone increases the myocardial glucose metabolism and shows a benefitial result to heart functions.     

Effect of atorvastatin on blood pressure in spontaneously hypertensive rats

AIM: To explore the mechanisms underlying the effect of atorvastatin on blood pressure in spontaneously hypertensive rats (SHR). METHODS: The effects of atorvastatin on plasma endothelin-1, aortic nitric oxide synthase, aortic smooth muscle cell (ASMC) apoptosis and p27 expression in SHR were evaluated. 12 eight-week-old SHR were randomized into atorvastatin group (ATV, n=6) and SHR group (n=6). 6 age-matched normotensive Wistar-Kyoto rats (WKY) were served as controls. 50 mg·kg-1·d-1 of atorvastatin was administered to ATV by gavage for 10 weeks. Serum cholesterol and triglycerides were measured, and systolic blood pressure of caudal artery was examined. Plasma endothelin-1 and nitric oxide synthase activity of aortic tissue were measured. ASMC apoptosis rate was detected by TUNEL technique, and positive expression rate of P27 in ASMC was analyzed. RESULTS: After 10 weeks, systolic blood pressure in ATV was significantly lower than that in SHR ［(134.17±3.60）mmHg vs （173.33±3.78）mmHg, P<0.01］. Compared with SHR, serum cholesterol and triglycerides were significantly lower (P<0.01, P<0.01) in ATV. Additionally，atorvastatin significantly decreased plasma endothelin-1 ［(130.04±40.07）ng/L vs （196.74±59.69）ng/L, P<0.05］ and increased nitric oxide synthase activity in aortic tissue ［(0.189±0.040）kU/g protein vs (0.124±0.057)kU/g protein, P<0.01］, compared with SHR. ASMC apoptosis rate was higher in ATV than that in SHR (16.94%±3.08% vs 9.01%±2.36%, P<0.01). Compared with WKY, positive expression rate of p27 in ASMC from ATV was higher (33.02%±5.01% vs 24.25%±4.41%, P<0.05), whereas that was lower in SHR (16.08%±7.09% vs 24.25%±4.41%, P<0.01). CONCLUSION: Atorvastatin may reduce the plasma endothelin-1， up-regulate nitric oxide synthase activity and ASMC P27 expression and facilitate ASMC apoptosis，which may effectively reduce blood pressure in SHR.     

早熟大粒无核葡萄新品种‘超级无核’

 ‘超级无核’葡萄系从美国引进葡萄新品种‘Superior Seedless’优选单株培育出的优良品种。无核、大粒、早熟、优质、早实、丰产、生长势强健、耐病、耐不利栽培条件, 是适合高温、高湿、少日照地区栽培的无核葡萄新品种。     

COX-2 inhibitor protects rat heart against oxidative stress through a pathway independent of cyclooxygenase

AIM: To investigate whether nimesulide ［a selective cyclooxygenase 2 (COX-2) inhibitor］ and piroxicam (an inhibitor of COX-1) protect the rat hearts against oxidative stress induced by hydrogen peroxide,superoxide anion or hydroxyl free radical.METHODS: Cardiac contractility,lactate dehydrogenase (LDH) and malondialdehyde (MDA) were analyzed by the Langendorff method in isolated rat hearts.Production of 6-Keto-PGF1α,a marker of COX activity,was measured in isolated rat hearts.RESULTS: Rat hearts were exposed to hydrogen peroxide (H₂O₂),pyrogallol (which produced superoxide anion) or Vit C+Fe2+ (which produced hydroxyl free radical) for 10 min followed by reperfusion for 30 min.H₂O₂ decreased cardiac contractility and increased LDH release,which was inhibited by nimesulide (3 mg/kg) ［LVDP 72%±10% vs 61%±11%,LDH （5.5±2.5）U/L vs （8.0±2.1）U/L,P<0.05］.Piroxicam (3 mg/kg) increased systolic function (LVDP 73%±10% vs 61%±11%,P<0.05),but exacerbated diastolic function ［LVEDP （29.00±5.61）mmHg vs （23.16±3.57） mmHg,P<0.01］ in H₂O₂ treated rat hearts.Nimesulide also protected rat hearts against superoxide anion and hydroxyl free radical injury.Nimesulide and piroxicam had no effect on the content of 6-Keto-PGF_1α in rat hearts.Mitochondrial ATP sensitive potassium channel (mitoK_ATP) inhibitor 5-HD blocked the improvement of contractility (LVDP and ±dp/dt_max) induced by nimesulide in H₂O₂ treated rat hearts (53%±12% vs 69%±3%,58%±11% vs 72%±7% and 37%±8% vs 51%±4% respectively,P<0.01).CONCLUSION: The results suggests that COX-2 inhibitor nimesulide can protect rat hearts against oxidative injury.The protection is independent of COX activity.Activation of mitoK_ATP may be involved in nimsulide-induced cardioprotection in rat hearts.     

Immune function of dendritic cells in patients with hepatocellular carcinoma

AIM: To investigate the immune function of dendritic cells (DCs) in patients with hepatocellular carcinoma(HCC). METHODS: The DCs were cultured from human peripheral blood mononuclear cells (PBMC) by using GM-CSF and IL-4 for 7 days. Surface molecules CD86, HLA-DR of DCs were detected by flow cytometry. IL-12 production by DCs and IFN-γ production by T cells was measured with ELISA and ELISPOT, respectively. Allogenic mixed lymphocyte reaction was detected by MTT assay. RESULTS: CD86 expression in DCs in HCC patients were markedly lower than that in health control (91.7％ vs 83.5%, P<0.05). IL-12 production by DCs had no significant difference between the HCC patients and the health control ［(324.6±171.0)ng/L vs (436.5±142.7)ng/L, P>0.05］. However, after stimulated DCs with LPS, IL-12 production in HCC patients was significantly lower than that in health control ［(478.6±142.7)ng/L vs (630.0±151.9)ng/L, P<0.05］. IFN-γ production by T cells and T cell proliferation index (PI) in the HCC patients were all significantly lower than those in health control ［(IFN-γ: 133.4±51.2)103U/L vs (183.0±60.2)103U/L, P<0.05; PI: 2.3±0.7 vs 3.5±0.8, P<0.01］. CTL killing activity assay indicated that DC-induced CTL killing activity in HCC group was significantly lower than that in health group when the E/T ratio was 10∶1 and 20∶1, respectively. CONCLUSION: The immune function of DCs and T cells in the patients with HCC are significantly decreased. The CTL killing activity of HCC group is also markedly decreased.     

Effect of pioglitazone on glucose metabolism and PPAR-γ expression in lipid-infused rats

AIM: To investigate the effect of pioglitazone (Pio) on glucose metabolism and peroxisome proliferators-activated receptor (PPAR)-γ expression in free fatty acid (FFA) -induced insulin resistance in rats. METHODS: A hyperinsulinaemic-euglycaemic clamp and ［3-3H］-glucose tracing technique were used in awake rats. Glucose metabolism in vivo and PPAR-γ in adipose tissue expression were assessed with elevation FFA by lipid infusion over 4 h in rats pretreated with or without Pio.RESULTS: During steady-state of clamp, there was a significant increase in plasma FFA in two lipid-infused groups, compared to control rats (P<0.01). The glucose infusion rates (GIR) in Pio-treated rats (P/L group), compared with controls, were significantly reduced ［(20.6±0.4) mg·kg^-1·min^-1 vs (33.6±0.6)mg·kg^-1· min^-1, P<0.01］, whereas the GIR was lower in the lipid group (L group) than that in the P/L group［(12.6±0.8) mg·kg^-1·min^-1 vs (20.6±0.4) mg·kg^-1·min^-1, P<0.01］. The hepatic glucose production (HGP) was significantly suppressed (85%) ［(18.3±2.1)mg· kg^-1·min^-1 (basal) vs (2.7±2.4)mg· kg^-1·min^-1, and (17.5±2.6) mg· kg^-1·min^-1 vs (2.6±1.0)mg· kg^-1·min^-1］, all P<0.01 during clamp in control and P/L groups. The suppressive effect of insulin on HGP was significantly blunted in L group［(17.3±2.1)mg· kg^-1·min^-1 vs (15.8±1.5)mg· kg^-1·min^-1］. The rate of glucose disappearance (GRd) was significantly reduced in two lipid-infused rats compared with controls［(26.6±1.6)mg· kg^-1·min^-1 and (23.2±0.9)mg· kg^-1·min^-1 vs (37.7±2.6)mg·kg^-1·min^-1,P<0.01］. The PPAR-γ expression of adipose tissue in P/L group was significantly upregulated. CONCLUSION: Lipid-infusion induces an acute insulin-resistance in vivo. Pio treatment upregulates the PPAR-γ of adipose tissue and suppresses HGP. Pio can protect partly against lipid-induced insulin resistance.     

Effects of splenectomy on CD4+ , CD8+ and spleen function in cirrhotic rats with portal hypertension

AIM:To investigate the effect of subtotal splenectomy on the expression of CD4+、CD8+ and tuftsin in cirrhosic rats with portal hypertension (PHT) . METHODS:Rats liver cirrhosis was induced by subcutaneous injection of 40% CCl4. Fifty rats were randomly divided into five groups (n=10). Group A:control rats;group B:PHT rats;group C:normal rats with total splenectomy;group D:PHT with total splenectomy and group E:PHT with subtotal splenectimy. The hepatic function, the expression of CD4+, CD8+, the ratio of CD4+ to CD8+ and tuftsin were analyzed at the fourth week after treatment. RESULTS:The expression of tuftsin ,the ratio of CD4+ to CD8+ was significantly decreased in PHT rats with total splenectomy compared with PHT rats ［（171±21） ng/L vs （433±44）ng/L,P<0.01;(2.01±0.22 vs 1.12±0.12),P<0.01］. In the group of PHT rats with subtotal splenectomy, the expression of tuftsin, the ratio of CD4+ to CD8+ was higher than those in the PHT rats with total splenectomy ［（434±42） ng/L vs （171±21） ng/L,P<0.01;（1.97±0.18 vs 1.12±0.12,P<0.01］, however, the hepatic function was not show difference（P>0.05）. CONCLUSION:Spleen and immune function is significantly improved in PHT rats after subtotal splenectomy, but the hepatic function is not changed significantly.     

Effect of rhSOD on pulmonary nuclear factor-kappa B and MIP-1α expression in meconium-induced acute lung injury

AIM: To evaluate the role and mechanisms of recombinant human superoxide dismutase (rhSOD) in meconium-induced acute lung injury (ALI) by evaluating pulmonary MIP-1α and NF-κB expression. METHODS: 24 health male Sprage-Dawley rats were randomized to 3 groups (8, each group), followed by intratracheal (IT) administration with (1) saline at 1 mL/kg (control group); (2) 20% human newborn meconium suspension at 1 mL/kg, followed by saline at 1 mL/kg (Mec/saline group); (3) 20% human newborn meconium suspension at 1mL/kg, followed by rhSOD at 20 mg/kg (Mec/rhSOD group). The animal was killed 24 h after treatment. The measurements included the bronchoalveolar lavage (BAL) cell count, RT-PCR analysis of pulmonary MIP-1α mRNA expression, Western blotting analysis of pulmonary NF-κB expression. RESULTS: Meconium-induced ALI was characterized by increased BAL cell count, increased expressions of pulmonary MIP-1α mRNA and NF-κB protein ［(4.68±1.40)×109 cells/L vs (0.53±0.19)×109 cells/L, 3.60±0.75 vs 1.56±0.33, 0.72±0.31 vs 0.23±0.12, respectively in control rats, all P<0.01］. IT administration of rhSOD early in the ALI rat significantly decreased meconium-induced BAL cell count ［(3.13±0.77)×109 cells/L vs (4.68±1.40)×109 cells/L in Mec/saline rats, P<0.01］, inhibited the expression of pulmonary MIP-1α mRNA (2.20±0.39 vs 3.60±0.75, in Mec/saline rats, P<0.01) and NF-κB protein (0.44±0.21 vs 0.72±0.31 in Mec/saline rats, P<0.05). CONCLUSION: The early IT administration of rhSOD in ALI rat following meconium aspiration protects lung from inflammatory injury through inhibiting meconium-induced pulmonary MIP-1α mRNA and NF-κB protein expression.     

Effects of beta2-adrenergic blocker on cytosolic Ca2+ in isolated cardiomyocytes of rats with myocardial infarction

AIM: To investigate if beta2-adrenergic receptors result in more Ca2+ load after myocardial infarction (MI), the effects of beta2-adrenergic blocker on cytosolic Ca2+ (［Ca2+］i) were studied. METHODS: Male Wistar rats underwent a ligation of left coronary artery (n=9) or a sham operation (n=3). Cardiomyocytes were dissociated at 2, 4 and 8 weeks after MI and ［Ca2+］i was measured via fura-2 fluorescence. The response of cardiomyocytes to isoproterenol (1 μmol/L) in the presence or absence of atenolol (1 μmol/L), beta2-adrenergic blocker ICI118,551 (0.1 μmol/L) or propranolol (1 μmol/L) was examined. RESULTS: ICI118,551 suppressed the increase in ［Ca2+］i induced by isoproterenol at 4 and 8 weeks after MI (24.5%±5.7% vs 57.8%±13.2%, P<0.01; 12.2%±7.9% vs 44.6%±11.3%, P<0.01), but had no effects in control and 2 weeks post-MI groups. It decreased ［Ca2+］i in control and the three post-MI groups by 14.3%, 7.9%, 57.6% and 72.6%, respectively. Atenolol had suppressive effects only in control and 2 weeks post-MI groups (P<0.05). Propranolol had suppressive effects in control and all three post-MI groups (P<0.01). CONCLUSION: Beta 2-adrenergic blocker ICI118,551 exerts negative effects on ［Ca2+］i after MI, and the effects dramatically increase with the progression of MI.     

Genistein downregulates survivin gene expression and induces apoptosis in hepatocellular carcinoma HepG2 cells

AIM: To probe into the role of 1, 4, 5-trisphosphate inositol (IP3) and survivin protein in apoptosis of HepG2 cells induced by genistein. METHODS: HepG2 cells were treated with 60 μmol/L genistein for 12 h, 24 h, 48 h and 72 h. IP3, survivin and apoptosis rate were assayed by IP3-［3H］ Birtrak assay, Western blotting and flow cytometry, respectively. RESULTS: IP3 in groups incubated for 12 h, 24 h, 48 h and 72 h with 60 μmol/L genistein were significantly lower than that in control (P<0.01) ［(12.0±1.4) pmol/106cells, (7.5±0.8) pmol/106 cells, (5.6±0.5) pmol/106cells, (3.3±0.6) pmol/106 cells， vs (29.2±0.6) pmol/106 cells］. V-survivin/ V-β-actin, which was the gray degree multiply area of survivin/the gray degree multiply area of β-actin in groups incubated for 12 h, 24 h, 48 h and 72 h with 60 μmol/L genistein, were significantly lower than that in control (P<0.01) ［（0.36±0.13, 0.33±0.03, 0.23±0.04, 0.18±0.04）， vs 0.63±0.06］. The apoptosis rate in groups incubated with 60 μmol/L genistein for 24 h, 48 h and 72 h was significantly higher than that in control （P<0.01） ［(7.4%±0.5%, 20.5%±2.0%, 30.7%±1.6%) vs 2.6%±0.1%］. CONCLUSION: Genistein induces apoptosis in HepG2 cells by reducing IP3 production and survivin protein expression.     

Effect of glucocorticoid-treated dendritic cells on asthmatic Th2 response

AIM: To investigate the effect of dexamethasone-treated dendritic cells (DCs) on Th2 cytokine production from autologous T cells in asthmatic patients and explore the mechanisms by studying the effect of dexamethasone on differentiation, maturation and function of DCs from patients with asthma. METHODS: Human peripheral blood monocyte-derived DCs generated from asthmatic patients and healthy subjects were cultured in the absence or presence of dexamethasone. The phenotypic characterization of DCs was analyzed by flow cytometry. The mature DCs were harvested, washed, and then cocultured in vitro with autologous T cells purified by a nylon cotton column. The DC-T coculture supernatants were collected after 72 h incubation and analyzed for levels of IL-5 and IFN-γ by ELISA. RESULTS: The concentrations of IL-5 in the culture supernatants of DC-T coculture were significantly up-regulated in patients with asthma compared with that in healthy controls ［(145.13±89.76) ng/L vs (50.28±22.37) ng/L, P<0.01］. The level of IFN-γ in the DC-T coculture supernatants tended to be decreased in asthmatic patients than that in healthy controls, although this difference did not achieve statistical significance ［(197.58±76.32) ng/L vs (220.46±65.34) ng/L, P>0.05)］. There were significantly decreased levels of IL-5 by autologous T cells primed by dexamethasone-treated mature DCs from asthmatic patients ［(45.39±19.61) ng/L vs (145.13±89.76) ng/L, P<0.01］, alterations not observed from healthy controls (P>0.05). IFN-γ production was decreased by autologous T cells primed by dexamethasone-treated mature DCs from both asthmatic patients and healthy controls ［asthma group: (40.21±22.89) ng/L vs (197.58±76.32) ng/L, P<0.01; healthy controls: (56.78±20.37) ng/L vs (220.46±65.34) ng/L, P<0.01］. Dexamethasone-treated DCs exhibited decreased expression of CD83 (P<0.01) and increased expression of CD14 (P<0.01) in both asthmatic patients and healthy controls. CONCLUSION: DCs of asthmatic patients induce a Th2-skewed cytokine production from autologous T cells. Dexamethasone-treated DCs inhibit the Th2 reactions, and this effect is probably mediated through the pathway that dexamethasone inhibits DCs maturation and skews the macrophage/DC balance towards the macrophage side and thus directs the development more towards the macrophage lineage.     

Experimental study on induction of atherosclerotic plaque instability in rabbits after transfer of wild-type p53 gene

AIM: To study the apoptotic role of wild-type p53 in induction of plaque instability in atherosclerotic rabbits. METHODS: Fifty-four New Zealand White rabbits underwent balloon-induced abdominal aortic wall injury and then were fed on a diet of 1% cholesterol. At the end of the eighth week, the rabbits were randomly divided into two groups: group A and group B. Recombinant adenovirus carrying p53 and β-galactosidase (LacZ) genes were injected in group A and B, respectively. Two weeks later, 10 rabbits each in group A and B was killed and the remaining rabbits all underwent pharmacological triggering with injection of Chinese Russell's viper venom and histamine. RESULTS: Compared with group B, p53 gene over-expression in group A resulted in a marked increase in number of positive apoptotic cells (2.5%±0.8% vs 1.0%±0.3%, P<0.05) and a significant decrease in vascular smooth muscle cells (47.5%±6.8% vs 80.4%±10.6%, P<0.01), the thickness of the fibrous cap ［(132.9±56.7）μm vs （181.8±59.7） μm, P<0.05］ and the cap/intima-media ratio (0.20±0.18 vs 0.21±0.11, P<0.05). CONCLUSION: Transfer of human wild-type p53 genes effectively promotes apoptosis of VSMCs in atherosclerotic plaques, which makes the plaques vulnerable to rupture.     

Development and evaluation for volume overload-induced and pressure overload-induced cardiac hypertrophy in rats

AIM: To compare the evaluations for the structure and function of the hypertrophic hearts induced by volume overload or pressure overload in rats. METHODS: Volume overload-induced cardiac hypertrophy was established by abdominal aortacaval fistula (ACF) and pressure overload-induced cardiac hypertrophy was developed by constriction of aorta (CA). The cardiac structure and function were analyzed by echocardiography, hemodynamic determination, heart weight measurement and histological examination. RESULTS: Heart weight of rats in all the operated groups was increased compared to the sham-operated groups. In 1-week ACF group, the internal diameter ［(0.67±0.03)cm vs (0.60±0.02)cm, P<0.01］ and volume of left ventricle increased ［(0.69±0.10)mL vs (0.50±0.04)mL, P<0.01］，relative wall thickness (RWT) decreased (0.46±0.05 vs 0.55±0.05, P<0.01), compared with the sham-operated group. In 1-week CA group, interventricular septal thickness ［(0.20±0.03)cm vs (0.16±0.02)cm, P<0.05］, left ventricular posterior wall thickness ［(0.20±0.03)cm vs (0.16±0.02)cm, P<0.01］, RWT (0.71±0.17 vs 0.56±0.12, P<0.05) and +dp/dtmax (4 886±1 304 vs 3 674±325, P<0.05) were all increased compared with the sham-operated group. In 2-week-groups, these parameters changed more significiantly. CONCLUSION: Cardiac structure and function could be evaluated by echocardiography and hemodynamic determination. RWT is a sensitive index for the cardiac hypertrophy induced by both volume overload and pressure overload.     

Effect of γ radioactive stent on proliferation and apoptosis of smooth muscle cells

AIM: To observe effect of γ radioactive ［103Pd］ stent on the proliferation and apoptosis of smooth muscle cells, the mechanism of radioactive stent preventing in-stent restenosis was explored. METHODS: Fifty male New Zealand rabbits were randomized into stent group and ［103Pd］ stent group. Control group was set up. The materials were harvested on 3, 7, 14, 28, 56 days after operation and the following investigation were carried out, including pathomorphology, immunohistochemistry, apoptosis (TUNEL) and in situ hybridization studies.RESULTS: ① The severity of the stenosis in ［103Pd］ stent group was less severe than that in stent group. It was most obvious on 56 th day (P<0.01). ② The expression of proliferating cell nuclear antigen(PCNA) of ［103Pd］ stent group was lower than that in stent group on 3 to 28 days. It was most obvious on 7th day, 16.35%±0.79% vs 24.36±0.55% (P<0.01). ③ TUNEL method showed that the ［103Pd］ stent group had much more apoptosis of VSMC than that in stent group. The highest rate of apoptosis appeared on day 7, 14.72%±0.53% vs 12.42%±1.13% (P<0.01). ④ By calculating the ratio of PCNA/apoptosis (P〖KG*6〗∶〖KG-*2〗A), a much lower ratio was seen in ［103Pd］-stent groups than that in stent group at 3 to 28 days. There was significant statistic difference (P<0.05). ⑤ For bcl-2/bax ratio, the result in ［103Pd］-stent group was lower than that in stent group at 3 to 28 days. There was significant statistic difference (P<0.05).CONCLUSION: γ radioactive stent inhibits the proliferation and accelerates apoptosis of injured media vascular smooth muscle cells. It decreases the ratio of proliferation to apoptosis and relieves the severity of restenosis.     

Meconium induces formation of nitrotyrosine and expression of inducible nitric oxide synthase in the rat lung

AIM: To evaluate the contribution of inducible nitric oxide synthase (iNOS) and nitrotyrosine to acute lung injury (ALI) in rats with meconium aspiration. METHODS: 16 health male Sprage-Dawley rats were randomized to control group and meconium group, followed by intratracheally administration of 1 mL/kg saline or 1 mL/kg 20% human newborn meconium suspension. The animals were killed after 24 h of treatment. The measurements included bronchoalveolar lavage fluid (BALF) cell count, pulmonary myoloperoxidase (MPO) activity and nitric oxide (NO) level. Western bloting was used to determine the expression of pulmonary nitrotyrosine-a specific “footprint” of peroxynitrite and iNOS. RESULTS: Compared to control group, the rats in the meconium group had increased BALF cell counts ［(4.04±1.01)×109cells/L vs （0.53±0.19)×109cells/L］, pulmonary MPO activity ［(1.49±0.22）U/g wet lung tissue vs (0.62±0.16) U/g wet lung tissue］, NO level ［(12.77±5.00） mmol/g protein vs （4.89±1.32) mmol/g protein］, increased expression of nitrotyrosine and iNOS (0.46±0.19 and 1.49±0.60 vs 0.15±0.04 and 0.09±0.04, respectively), all P<0.01. CONCLUSIONS: Meconium results in an increase in expression of pulmonary iNOS, leading to over production of NO and nitrotyrosine, which may be of pathogenic importance in the ALI with meconium aspiration.     

Effects of salvianolic acid B on the energy metabolism and hydrocephalus in mice with cerebral ischemia

AIM: To explore the effects of salvianolic acid B (SalB) on the energy metabolism and hydrocephalus in mice with cerebral ischemia.METHODS: NIH mice were randomly divided into four groups: sham-operated group,cerebral ischemia group,SalB-treated group and nimodipine-treated group.The brain tissue energy charge (EC),phosphocreatine (PCr),the activity of ATPase,excitability amino acid (EAA) content and water content of brain were measured when cerebral ischemia for 30 min.RESULTS: EC (0.520±0.034),PCr content ［(98.344±13.249) μmol/g］,the activity of Na⁺-K⁺-ATPase ［(0.593±0.013)×10³ U/g］ and Ca²⁺-ATPase ［(0.484±0.053)×10³ U/g］ in SalB-treated group were significantly higher than those in cerebral ischemia group {EC (0.465±0.037),PCr content ［(81.614±9.919) μmol/g］ ,the activity of Na⁺-K⁺-ATPase ［(0.244±0.065)×10³ U/g］,the activity of Ca²⁺-ATPase ［(0.321±0.086)×10³ U/g］} (P<0.01).The glutamate (Glu) content ［(0.405±0.110) μmol/g］,aspartate (Asp) content ［(0.141±0.020) μmol/g］ and water content of brain ［(38.1±0.1)%］ in SalB-treated group were markedly lower than those in cerebral ischemia group ［ Glu content (0.550±0.140) μmol/g,Asp content (0.287±0.050) μmol/g,water content of brain (44.1±0.1)%］ (P<0.05,P<0.01).CONCLUSION: The increase in cerebral energy metabolism and the activity of ATPase,and decrease in EAA content in brain tissue are the mechanism of SalB alleviating hydrocephalus at the early stage of cerebral ischemia in mice.     

Effect of tachykinin on cough response in an ovalbumin-sensitized guinea pig model

AIM: To investigate the role of tachykinin in airway in cough response in guinea pigs sensitized and challenged with ovalbumin. METHODS: 20 normal and 20 sensitized guinea pigs were challenged with the aerosol of ovalbumin. twenty-four hours later, cough response to inhaled capsaicin was measured after the normal and sensitized guinea pigs (10 of each) introperitoneally injected either with 0.1 mg/kg, 0.3 mg/kg and 1.0 mg/kg of NK1 antagonist SR140333 or NK2 antagonist SR48968, respectively. Specific airway resistance was recorded with noninvasive technique. RESULTS: Cough response increased in sensitized guinea pigs compared with control ［(19.5±5.7） times/3 min vs （9.3±1.2） times/3 min, P<0.05］. SR48968FR decreased the cough response by 30% in control guinea pigs (P<0.05), but SR140333 did not. Both prevented an increase in airway resistance after the inhalation of capsaicin. However, SR48968FR and SR140333 inhibited increased cough response ［(9.9±4.7） times/3 min, （8.0±1.6） times/3 min, P<0.05］ and airway resistance induced by the inhalation of capsaicin. CONCLUSION: Neurokinin (NK) antagonist inhibits increased cough response in guinea pigs sensitized and challenged with ovalbumin. Tachykinin may be an important mediator in cough associated with eosinophilic airway inflammation.