厄贝沙坦对糖尿病大鼠肾小球PPAR-γ转录活性的影响

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。

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.