徐静琳　孔祥静　　韩颖敏　　陶海英

[关键词] 舒洛地特;微小RNA-27a;自噬;糖尿病肾病;足细胞损伤

[中图分类号] R285.5;R587.205          [文献标识码] A          [文章编号] 1673-9701（2021）14-0039-06

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

XU Jinglin1   KONG Xiangjing1   HAN Yingmin1   TAO Haiying2

1.Department of Nephrology， the First People′s Hospital of Taizhou City in Zhejiang Province， Taizhou   318000， China; 2.Department of Endocrinology， the First People′s Hospital of Taizhou City in Zhejiang Province， Taizhou 318000， China

[Abstract] 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.

[Key words] Sulodexide; miR-27a; Autophagy; Diabetic nephropathy; Podocyte injury

随着人们生活水平的不断提高，糖尿病及其并发症的发病率呈逐年上升的趋势，严重影响人们的生活质量，其中糖尿病肾病（Diabetic kidney disease，DKD）是糖尿病最严重的微血管并发症之一，目前已成为导致终末期肾病（End-stage renal disease，ESRD）的主要原因之一[1-2]。有数据显示[3]，我国DKD的患病率为20%～40%，此病起病较为隐匿，一旦进入大量蛋白尿期后，进展至ESRD的速度显著加快，因此，早期诊断、预防与延缓DKD的发生发展对提高DKD患者存活率、改善其生活质量具有重要意义。有研究显示[4]，微小RNA-27a（microRNA-27a，miR-27a）在DKD患者体内呈异常高表达，可刺激系膜细胞外基质合成增加即降解减少，加重DKD进展。目前临床研究证实[5]，舒洛地特是从动物小肠分离提取沉淀而成的一种天然血管壁糖胺聚糖，具有较高的血管趋向性且对糖尿病尿蛋白的发生具有防治作用。但miR-27a在DKD中的调控机制尚未十分清楚，故本研究旨在探讨舒洛地特调控miR-27a介导自噬调控糖尿病肾病足細胞损伤机制，现报道如下。

1 资料与方法

1.1 一般资料

选取45只雄性SPF级大鼠，购自冠科生物技术（中山）有限公司，动物许可证号：SYXK（粤）2020-0240，平均体重（218.63±32.45）g，在相对湿度为30%～35%、平均温度（23.8±1.5）℃下饲养1周，每日光照24 h。本实验操作均严格参照动物实验伦理要求相关规定进行，且获得我院医学伦理委员会审批同意。

1.2方法

1.2.1 仪器及试剂  血糖仪、血糖试纸购自上海信帆生物科技有限公司;普通光学……