miR-26a在糖尿病肾病大鼠肾脏的表达及其意义

EXPRESSION OF MICRORNA-26A IN THE KIDNEY OF RATS WITH DIABETIC NEPHROPATHY AND ITS SIGNIFICANCE

目的探讨microRNA-26a(miR-26a)在糖尿病肾病(DN)中的表达及其与DN的关系。方法高脂高糖喂养联合腹腔注射小剂量链脲霉素构建大鼠2型糖尿病模型(T2DM),另设正常对照(NC)组。于动物模型建立后8周收集两组大鼠血、尿及肾脏标本。比较两组血、尿生化指标,苏木精-伊红染色观察肾小球病理变化,实时定量PCR方法检测肾脏miR-26a、NephrinmRNA表达水平,WesternBlot方法测定肾脏Nephrin蛋白表达水平。结果与NC组比较,T2DM组大鼠空腹血糖(FBG)、胆固醇(TC)、三酰甘油(TG)、内生肌酐清除率(Ccr)、24h尿蛋白定量均明显升高(t=10.710~28.421,P<0.05)。光镜下观察,T2DM组肾小球体积较NC组增大,基底膜增厚,系膜区扩大,肾小球毛细血管腔受压变窄。与NC组比较,T2DM组NephrinmRNA和miR-26a表达明显减少(t=9.070、12.270,P<0.05),Nephrin蛋白表达明显减少(t=7.429,P<0.05)。Pearson分析显示,miR-26a与Nephrin表达正相关(r=0.650,P<0.01)。结论miR-26a在DN大鼠肾组织表达降低,并与大鼠DN足细胞的损伤密切相关。

Objective To investigate the expression of microRNA-26a (miR-26a) in diabetic nephropathy (DN) and its relationship with DN. Methods A rat model of type 2 diabetes mellitus (T2DM) was established by high-fat and high-sugar diet combined with intraperitoneal injection of low-dose streptozotocin, and a normal control (NC) group was also established. Blood, urine, and kidney specimens were collected at 8 weeks after the establishment of the animal model. The blood and urine biochemical parameters were compared between the two groups. Glomerular pathology was observed by HE staining. The expression of miR-26a and Nephrin mRNA was determined by qPCR, while the protein expression of Nephrin in the renal cortex was measured by Western blot. Results Compared with the NC group, the T2DM group had significantly increased fasting blood glucose, cholesterol, triglyceride, endogenous creatinine clearance, and 24 h urinary protein excretion ( t =10.710-28.421, P <0.05). As observed under light microscopy, the T2DM group had a larger glomerular volume, a thicker basement membrane, an enlarged mesangial region, and a smaller glomerular capillary lumen compared with the NC group. Meanwhile, the T2DM group had significant reductions in the expression of Nephrin mRNA and miR-26a ( t =9.070,12.27;P <0.05), as well as Nephrin protein ( t =7.429, P < 0.05), as compared with the NC group. Pearson analysis showed that miR-26a was positively correlated with the expression of Nephrin ( r =0.650, P <0.01). Conclusion In rats with DN, the expression of miR-26a in renal tissue is reduced, which is closely associated with the damage of podocytes.