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目的:探讨microRNA-26a-5p（miR-26a-5p）对糖尿病肾脏疾病（diabetic kidney disease，DKD）足细胞损伤的保护作用及其机制。方法:（1）体内实验：4周龄db/db小鼠按数字表法被分为db/db组、db/db+agomir-NC组、db/db+miR-26a-5p agomir组，每组10只，设同周龄db/m小鼠10只作为正常对照组。饲养至10周龄时观察各组小鼠肾组织病理改变，检测肾脏肥大指数（kidney weight/body weight，KW/BW）、空腹血糖（fasting blood glucose，FBG）和尿白蛋白肌酐比（urinary albumin to creatinine ratio，ACR）等指标；采用荧光原位杂交法观察miR-26a-5p的定位，实时荧光定量PCR法测定肾组织miR-26a-5p水平，免疫组化及Western印迹法测定瞬时受体电位阳离子通道蛋白6（transient receptor potential cation channel-6，TRPC6）和Nephrin表达。（2）体外实验：小鼠足细胞（MPC5）被分为正常糖组、高渗组、高糖组、高糖+miR-26a-5p mimic组和高糖+mimic-NC组共5组，测定各组足细胞miR-26a-5p及TRPC6和Nephrin蛋白的表达水平，通过荧光素酶报告基因实验验证miR-26a-5p和TRPC6 mRNA的靶向结合关系。结果:（1）体内实验：与db/m小鼠相比，db/db小鼠肾组织光镜下见肾小球体积增大，电镜下见基底膜增厚，足突融合率增加，ACR、FBG和血脂升高（均n P<0.01），miR-26a-5p及Nephrin表达减少（均n P<0.05），而TRPC6表达增多（n P<0.05）；与db/db+agomir-NC组相比，db/db+miR-26a-5p agomir组小鼠肾脏病理改变减轻，肾组织TRPC6表达和ACR降低（均n P<0.05），Nephrin表达增多（n P<0.05）。（2）体外实验：与正常糖组比较，高糖组足细胞miR-26a-5p表达减少（n P<0.01），Nephrin表达减少而TRPC6表达增多（均n P<0.05）；与高糖+mimic-NC组比较，高糖+miR-26a-5p mimic组足细胞TRPC6表达减少（n P<0.05），Nephrin表达增加（n P<0.05）；荧光素酶实验提示miR-26a-5p靶向调节TRPC6表达。n 结论:DKD足细胞中miR-26a-5p表达减少，miR-26a-5p可以通过抑制TRPC6表达减轻DKD足细胞损伤。“,”Objective:To investigate the protective effect and potential mechanisms of microRNA-26a-5p (miR-26a-5p) on podocyte injury in diabetic kidney disease (DKD).Methods:(1) n In vivo experiment: Four-week-old db/db mice were divided into db/db group, db/db+agomir-NC group and db/db+miR-26a-5p agomir group according to random number table method, with 10 mice in each group, and 10 db/m mice of the same week-old were set as normal control group. At the age of 10 weeks, pathological changes were observed through light and electron microscopy. Kidney weight/body weight (KW/BW), urinary albumin to creatinine ratio (ACR), fasting blood glucose (FBG) and other biochemical indicators were also detected. The position and expression of miR-26a-5p in kidney tissue were determined through fluorescence n in situ hybridization and quantitative real-time PCR, while the expressions of transient receptor potential cation channel-6 (TRPC6) and Nephrin in kidney tissue were determined by Western blotting and immunohistochemistry. (2) n In vitro experiment: The immortalized mouse podocytes (MPC5) were divided into 5 groups: normal glucose group, high mannitol group, high glucose group, high glucose+miR-26a-5p mimic group, and high glucose+mimic-NC group. The expressions of miR-26a-5p, TRPC6 and Nephrin were detected. Luciferase reporter assay was conducted to research the relationship of miR-26a-5p and TRPC6.n Results:(1) n In vivo experiment: Compared with db/m group, db/db mice exhibited lower KW/BW and disrupted conditions of ACR, FBG, total cholesterol, triglycerides and low density lipoprotein cholesterol (all n P<0.01). Increased glomeruli volume, more extracellular matrix deposition, thicker basement membrane and more foot process fusion were observed by light and electron microscope. Increased expression of TRPC6 protein as well as decreased expression of Nephrin protein and miR-26a-5p were detected in kidney tissues of db/db mice (n P<0.05). Compared with db/db+agomir-NC group, db/db mice transfected by miR-26a-5p agomir exhibited less albuminuria, with less protein expression of TRPC6 and more Nephrin in kidney tissue (alln P<0.05). (2)n In vitro experiment: Compared with normal glucose group, high glucose-treated podocytes exhibited increased expression of TRPC6 (n P<0.05), as well as decreased expression of Nephrin (n P<0.05) and miR-26a-5p (n P<0.01). Compared with high glucose+mimic-NC group, lower expression of TRPC6 and higher expression of Nephrin were detected in podocytes transfected by miR-26a-5p mimic (bothn P<0.05). Luciferase reporter assay confirmed that miR-26a-5p could regulate the expression of TRPC6 precisely.n Conclusions:The expression of miR-26a-5p in podocytes is down-regulated in the context of high glucose and miR-26a-5p protects podocytes from injury via inhibiting the expression of TRPC6 in DKD.