糖尿病大鼠肾皮质ICAM-1在缬沙坦作用后表达的变化研究

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目的:利用血管紧张素I(IAngII)受体拮抗剂缬沙坦(Valsartan)阻断肾素-血管紧张素(RAS)观察其对糖尿病大鼠肾皮质细胞间粘附分子-1(ICAM-1)表达的影响。方法:成年雄性SD大鼠45只,任取其中30只腹腔注射链脲佐菌素制成糖尿病大鼠模型。将糖尿病大鼠随机分为糖尿病缬沙坦治疗组(A组,15只,缬沙坦10mg.kg-1/d灌胃);糖尿病对照组(B组,15只);其余15只为正常对照组(C组)。分别于实验第4、6周末各组任取7或8只测定大鼠血糖、平均动脉压、血肌酐、尿肌酐、尿白蛋白排泄率,用图像分析仪测量各组大鼠平均肾小球面积、平均肾小球体积。并于第6周末取各组大鼠肾皮质提取RNA,用逆转录-PCR(RT-PCR)方法对肾皮质ICAM-1mRNA表达进行半定量分析。结果:在第4周及第6周末,A组血糖、肌酐清除率、尿白蛋白排泄率显著低于同时期的B组,B组则较C组均有不同程度的升高(P<0.01),A、C组尿白蛋白排泄率始终无统计学差异,同时期三组平均动脉压无统计学差异(P>0.05)。在4、6周,A、B组的肾小球平均面积、平均体积均明显高于同期的C组(P<0.01),但A组又低于同期的B组。RT-PCR半定量结果分析显示,B组ICAM-1 mRNA表达较A、C组显著增高(P<0.01),A组表达较C组为高(P<0.01),但仍较B组为低(P<0.01)。结论:血管紧张素I(IAngII)受体拮抗剂缬沙坦能够减少糖尿病大鼠的尿白蛋白排泄,下调肾皮质ICAM-1mRNA表达,减轻肾脏肥大及延缓肾小球硬化,具有保护肾脏的作用。 OBJECTIVE: To investigate the effect of Valsartan on renal interstitial cell adhesion molecule-1 (ICAM-1) in diabetic rats by blocking renin-angiotensin (RAS) by angiotensin I (IAngII) ) Expression. Methods: Forty-five male Sprague-Dawley rats were randomly divided into three groups: 30 diabetic rats were injected intraperitoneally with streptozotocin. The diabetic rats were randomly divided into diabetic valsartan treatment group (group A, 15, valsartan 10mg.kg-1 / d gavage); diabetic control group (group B, 15); the remaining 15 were normal Control group (C group). At the end of the 4th and 6th week of the experiment, 7 or 8 rats in each group were taken to measure blood glucose, mean arterial pressure, serum creatinine, urinary creatinine and urinary albumin excretion rate. The mean glomerular Area, average glomerular volume. At the end of the sixth week, RNA was extracted from the renal cortex of each group, and ICAM-1 mRNA expression in renal cortex was semi-quantitatively analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Results: The blood glucose, creatinine clearance rate and urinary albumin excretion rate in group A were significantly lower than those in group B at the end of the 4th and 6th week, while those in group B were all increased to some extent (P <0.01) ), Urinary albumin excretion rate in group A and group C had no statistical difference at the same time, mean arterial pressure in the three groups had no significant difference (P> 0.05). At 4 and 6 weeks, the mean area and average volume of glomeruli in group A and group B were significantly higher than those in group C (P <0.01), but were lower in group A than in group B at the same period. Semiquantitative RT-PCR results showed that the expression of ICAM-1 mRNA in group B was significantly higher than that in group A and C (P <0.01), and the expression of ICAM-1 mRNA in group A was significantly higher than that in group C (P <0.01) (P <0.01). Conclusion: Valsartan, an angiotensin I receptor antagonist, can reduce urinary albumin excretion, reduce ICAM-1 mRNA expression in renal cortex, reduce renal hypertrophy and delay glomerulosclerosis, and has a protective effect on the kidneys .
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