厄贝沙坦对糖尿病肾脏疾病大鼠肾脏miR-93及其相关蛋白表达的影响

Effect of Irbesartan on the expression of renal miR-93 and related proteins in diabetic kidney disease rats

目的观察厄贝沙坦对STZ诱导的DKD大鼠肾脏miR-93及其相关蛋白表达的影响,探讨ARB类药物治疗DKD的可能机制。方法40只雄性Wistar大鼠随机分为正常对照(NC)组10只和实验组30只。腹腔注射小剂量STZ(28 mg/kg)建立DKD大鼠模型。造模成功的20只大鼠分为DKD模型组(DKD)及厄贝沙坦治疗组(IRB),每组各10只。于22周检测大鼠体重、FBG、24 hUAlb等。镜下观察肾脏形态学改变。采用qRT-PCR及Western blot、免疫组织化学法检测肾脏miR-93及VEGF、纤维连接蛋白(FN)、4型胶原蛋白(CollagenⅣ)的表达情况。结果与NC组比较,DKD组FBG、24 hUAlb升高(P<0.05),IRB组低于DKD组(P<0.05)。与NC组比较,DKD组miR-93表达下调(P<0.05),VEGF、FN、CollagenⅣ表达升高(P<0.05)。与DKD组比较,IRB组miR-93表达上调(P<0.05),VEGF、FN及CollagenⅣ表达降低(P<0.05)。结论miR-93可能参与DKD大鼠肾脏的保护作用,厄贝沙坦可能通过影响miR-93及相关蛋白表达而发挥肾脏保护作用。

ObjectiveTo investigate the effect of Irbesartan on the expression of miR-93 and its related proteins in kidneys of rats with STZ-induced diabetic nephropathy(DKD),and to explore the possible mechanism of ARBs in the treatment of DKD.into normal control group(NC,n=10),diabetic nephropathy model group(DKD,n=10)and Irbesartan treatment group(IRB,n=10). The diabetic nephropathy rat model was established by intraperitoneal injection of small dose STZ(28 mg/kg). At 22 weeks,laboratory indexes such as weight,fasting blood glucose and 24-hour urine protein were tested. The morphological changes of kidney were observed under light microscope. qRT-PCR,Western blot and Immunohistochemistry were used to detect the expression of miR-93,and the protein of vascular endothelial growth factor(VEGF),fibronectin(FN)and collagen type 4(CollagenⅣ)in the kidney.ResultsThe levels of FBG and 24-hour urine protein were higher in DKD group than in NC group(P<0. 05). The above indexes were lower in IRB group than in DKD group(P<0. 05). Compared with NC group,the expression of miR-93 was down-regulated in DKD group(P<0. 05),while the expression of VEGF,FN and Collagen Ⅳ proteins were up-regulated in DKD group(P<0. 05). Compared with DKD group,the expression of miR-93 was up-regulated,while the expression of VEGF,FN and Collagen IV proteins were decreased in IRB group(P<0. 05).ConclusionmiR-93 may be involved in renal protection in DKD rats,and Irbesartan may play a role in renal protection by affecting the expression of miR-93 and its related proteins.