糖尿病大鼠肾皮质ICAM-1在缬沙坦作用后表达的变化研究

Effect of Angiotensin II Receptor Antagonist on Expression of ICAM-1 in Renal Cortex of Experimental Diabetic Rats

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 mechanism of Valsartan in protecting the kidney of streptozotocin-induced diabetic rats. Methods： Sprague-dawley rats were randomly divided into diabetic model treated with Valsartan （10mg. kg-~/d）group（A）, diabetic model group （B） and normal control group （C）. Plasma glucose, kidney mass/body mass ratio, MAP, serum creatinine, urinary creatinine, 24 urinary albumin excretion ratio were measured in the 4th, 6th week respectively. ICAM-1 mRNA expression in renal cortinal were measured with RT-PCR in the 6th week. And the kidney sample were observed with light and electron microscope. Mean glomerular transverse sectional area and mean glomerular volume were calculated by analysis system of the image. Results： In both two stages, kidney mass/body mass ratio, Ccr, 24 urinary albumin excretion ratio in both diabetic group （B） were higher than that of normal group（C） （P〈0.01）, but they were decreased significantly in A group than that in B group. For the urinary albumin in two stages, there was no difference between A and C group （P〉0.05）. In the 4th and 6th, the MGPA and MGV in group A were significantly smaller than that of B group （P〈0.01）. ICAM-1 mRNA expression were higher in B group than that in A and C group. Conclusion： Valsartan could reduce the expression of ICAM-1 mRNA, it could reduce the level of nrinary albumin and could prevent the glomerular sclerosis, so the pathological progress of kidney was delayed in diabetic rats.