厄贝沙坦对糖尿病大鼠肾小球PPAR-γ转录活性的影响

摘要

Objective To investigate the effects of irbesartan on transcription activity of peroxisome proliferators-activated receptorγin the kidney glomeruli of diabetic rats and further investigate the possible mechanisms. Methods Male SD rats were randomly divided into three groups as followed:normal control group,diabetic group,Irbesartan treated diabetic group.Diabetic rats model were induced by intraperitoneal injection of streptozotocin. After 12 weeks,24-hour urinary protein was quantified,ECM was measured by PAS staining,expression of p-ERK in glomeruli was detected by immunohistochemistry,and mRNA expressions of PPAR-γand A-FABP in glomeruli were semi-quantified by RT-PCR assay,mRNA expression level of A-FABP was regarded as the index of PPAR-γtranscription activity.Results Treatment with irbesartan decreased 24-hour urinary protein excretion and glomerular ECM deposition in diabetic rats. Although the PPAR-γmRNA level has not significant variance between diabetic group and Irbesartan treated group,the expression level of p-ERK protein decreased,and PPAR-γtranscription activity increased remarkably in Irbesartan treated group. Conclusions Treatment with irbesartan ameliorates renal lesions in diabetic rats and increases PPAR-γtranscription activity possibly by inhibiting p-ERK expression.%目的：观察厄贝沙坦对糖尿病大鼠肾组织过氧化物酶体增殖物激活受体γ（PPAR-γ）转录活性的影响，并对相关机制进行初步探讨。方法雄性SD大鼠分为3组：正常对照组、糖尿病对照组、糖尿病厄贝沙坦治疗组。采用STZ腹腔注射制成糖尿病模型。各组大鼠饲养12周后测24h尿蛋白量，分别采用PAS染色观察肾小球细胞外基质（ECM）沉积，免疫组化染色检测肾小球p-ERK蛋白的表达，RT-PCR检测肾小球PPAR-γ和A-FABP mRNA的相对表达量，以A-FABP mRNA的表达水平代表PPAR-γ的转录活性。结果与糖尿病对照组比较，厄贝沙坦治疗组大鼠肾小球PPAR-γmRNA水平无明显变化，但肾小球p-ERK表达减少，肾小球PPAR-γ的转录活性明显增强，24h尿蛋白量与肾小球ECM沉积明显减少。结论厄贝沙坦改善糖尿病大鼠肾脏病变，增强糖尿病大鼠肾小球PPAR-γ的转录活性。机制可能与其减轻p-ERK对PPAR-γ转录活性的抑制有关。