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目的观察整合素α3β1在糖尿病大鼠肾小球的表达以及替米沙坦对其影响。方法制备糖尿病大鼠模型,随机将动物分为糖尿病组、治疗组,另设对照组。治疗组给予替米沙坦3mg·kg--·d-1。6周后,检测各组24h尿白蛋白定量、肌酐清除率、血糖、血胰岛素、血压、肾重/体重;免疫组化法检测肾小球整合素α3β1表达部位及表达水平。分离肾小球,Western印迹法检测肾小球整合素α3β1蛋白表达水平。RT-PCR检测肾小球TGF-β1mRNA的表达。光镜下观察肾组织病理改变;电镜下观察肾组织超微结构变化。结果免疫组化结果显示,正常大鼠整合素α3β1主要沿肾小球血管袢呈线性表达,系膜区有少量表达。糖尿病组肾小球整合素α3β1表达比正常对照组明显减弱;替米沙坦治疗组整合素α3β1表达较糖尿病组明显增加,24h尿白蛋白定量及其它肾功能指标以及病理改变明显改善,血压无明显变化,肾小球TGF-β1mRNA表达比糖尿病组显著下降。结论替米沙坦可以减少糖尿病肾病大鼠早期的尿蛋白,改善病理变化,保护肾功能,其作用机制可能部分通过减少TGF-β1表达,上调整合素α3β1表达而实现。
Objective To observe the expression of integrin α3β1 in the glomerulus of diabetic rats and the effect of telmisartan on it. Methods Diabetic rat model was established. Animals were randomly divided into diabetic group, treatment group and another control group. The treatment group was given telmisartan 3mg · kg-- · d-1.6 weeks after the detection of 24h urine albumin, creatinine clearance, blood glucose, blood insulin, blood pressure, kidney weight / body weight; immunohistochemistry Detection of glomerular integrin α3β1 expression and expression levels. Glomeruli were isolated and the expression of glomerular integrin α3β1 protein was detected by Western blotting. The expression of TGF-β1 mRNA in glomerulus was detected by RT-PCR. The pathological changes of renal tissues were observed under light microscope. The ultrastructural changes of renal tissues were observed under electron microscope. Results The results of immunohistochemistry showed that the expression of integrin α3β1 in glomeruli was linear and the mesangial area was slightly expressed. Compared with normal control group, the expression of integrin α3β1 in diabetic group was significantly weaker than that in normal control group. The expression of integrin α3β1 in diabetic group was significantly higher than that in diabetic group, the urinary albumin in 24h and other renal function indexes and pathological changes were significantly improved, Significant changes, glomerular TGF-β1mRNA expression was significantly lower than the diabetic group. Conclusion Telmisartan can reduce urinary protein, improve pathological changes and protect renal function in rats with diabetic nephropathy. Its mechanism may be partly through reducing the expression of TGF-β1 and up-regulating the expression of integrin α3β1.