舒洛地特调控miR-27a介导自噬调控糖尿病肾病足细胞损伤机制研究

目的分析舒洛地特调控微小RNA-27a(miR-27a)介导自噬调控糖尿病肾病足细胞损伤的机制。方法选取45只中15只大鼠作为正常组不做任何处理,其余大鼠建立糖尿病肾病大鼠模型,随机分为模型组、舒洛地特组各15只。舒洛地特组大鼠给予舒洛地特肌内注射,正常组和模型组给予等体积生理盐水肌内注射。观察各组大鼠病理组织学变化,血糖、血脂和肾功能指标、足细胞自噬体情况、凋亡率,足细胞特异性蛋白Nephrin、Desmin、GPR124及miR-27a、AMPK-mTOR信号通路蛋白表达量。结果舒洛地特组血糖、血脂和肾功能指标、足细胞凋亡率、Desmin、miR-27a、AMPK-mTOR信号通路蛋白表达量均低于模型组,差异有统计学意义(P0.05)。舒洛地特组足细胞自噬体数量、Nephrin、GPR124蛋白表达量均高于模型组,差异有统计学意义(P0.05)。结论舒洛地特可通过下调miR-27a介导AMPK、mTOR、Bax蛋白表达量降低,进而抑制AMPK-mTOR信号通路,促进糖尿病肾病足细胞自噬、抑制糖尿病肾病足细胞凋亡、减轻糖尿病肾病足细胞损伤。

Mechanism research of sulodexide in regulating miR-27a-mediated autophagy in regulation of podocyte injury in diabetic nephropathy

Objective To analyze the mechanism of sulodexide in regulating microRNA-27a (miR-27a)-mediated autophagy in the regulation of podocyte injury in diabetic nephropathy.Methods Fifteen of the 45 rats were selected as the normal group without any treatment,and the remaining rats were used to establish a diabetic nephropathy rat model and randomly divided into the model group and the sulodexide group with 15 rats in each group.Rats in the sulodexide group were given intramuscular injection of sulodexide,while those in the normal group and the model group were given intramuscular injection of equal volume of normal saline.Histopathological changes,blood glucose,blood lipid and renal function indexes,podocyte autophagosome status,apoptosis rates,and podocyte specific protein expression levels,including Nephrin,Desmin,GPR124,miR-27a and AMPK-mtor signaling pathway protein were observed.Results The blood glucose,lipid and renal function indexes,podocyte apoptosis rates,Desmin,miR-27a and AMPK-mtor signaling pathway protein expression levels in the sulodexide group were lower than those in the model group,with significant difference (P<0.05).The number of podocyte autophagosomes,the protein expression of Nephrin and GPR124 in the sulodexide group were higher than those in the model group,with significant difference (P<0.05).Conclusion Sulodexide can mediate the reduction of the expression of AMPK,mTOR and Bax proteins by decreasing miR-27a,and then inhibit the AMPK-mTOR signaling pathway,promote autophagy,inhibit apoptosis and reduce the injury of podocytes in diabetic nephropathy.