基于miR⁃26a/TRPC6轴探究六味地黄汤对糖尿病肾病大鼠肾脏保护作用机制  

Renoprotective effect and mechanism of Liuwei Dihuang Decoction on diabetic nephropathy in a rat model based on miR26a/TRPC6 axis

作　　者：李杨 温伟波 LI Yang;WEN Weibo(Yunnan Provincial Hospital of Traditional Chinese Medicine/The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine,Kunming 650000,China;Department of Traditional Chinese Medicine,Yunnan Women and Children's Hospital,Kunming 650000,China)

机构地区：[1]云南省中医医院/云南中医药大学第一附属医院,云南昆明650000 [2]云南省妇幼保健院中医科,云南昆明650000

出　　处：《海南医科大学学报》2025年第3期185-192,共8页Journal of Hainan Medical University

基　　金：云南省科技厅科技计划项目(202101AZ070001-068)。

摘　　要：目的:探讨六味地黄汤改善糖尿病肾病大鼠的作用机制。方法:八周龄雄性SD大鼠60只,体质量180~220 g,随机分为6组(n=10),即正常组、模型组、六味地黄汤低剂量组,六味地黄汤中剂量组,六味地黄汤高剂量组以及厄贝沙坦处理组。正常组常规饲料喂养,联合一次性等剂量枸橼酸缓冲液腹腔注射。其余50只采用高脂饲养加一次性注射链脲佐菌素造模。造模成功后,给予六味地黄汤灌胃治疗,阳性对照使用厄贝沙坦处理。给药结束后先收集24 h尿液,生化法检测尿蛋白含量;ELISA检测空腹血糖、肌酐含量,检测大鼠血清中炎性因子白细胞介素6(IL-6)和白细胞介素1β(IL-1β)水平。大鼠称重,处死,分离双肾组织,苏木素-伊红(H&E)染色观察各组大鼠肾脏组织变化;qPCR检测miR-26a表达水平;Western blot和免疫组化检测肾脏组织中TRPC6表达。结果:与正常组比较,模型组中空腹血糖、24 h尿蛋白、肌酐水平明显升高,体重降低,肾指数升高,炎性因子IL-6和IL-1β表达显著升高,miR-26a表达降低,TRPC6表达水平升高(P<0.05),模型组大鼠中肾组织损伤严重;与模型组比较,六味地黄汤灌胃处理后,空腹血糖、24 h尿蛋白、肌酐水平降低,体重升高,肾指数降低,炎性因子IL-6和IL-1β表达降低,miR-26a表达增强,TRPC6表达受到抑制(P<0.05),大鼠肾组织损伤得到改善,且高剂量组改善效果优于低剂量组。结论:六味地黄汤可能通过miR-26a/TRPC6分子轴改善大鼠糖尿病肾病。Objective:To investigate the mechanism of Liuwei Dihuang Decoction in improving diabetic nephropathy rats.Methods:A total of 60 eight-week-old male SD rats,weighing 180~220 g,were randomly divided into 6 groups(n=10),including the normal group,the model group,the Liuwei Dihuang Decoction low-dose group,the Liuwei Dihuang Decoction mediumdose group,the Liuwei Dihuang Decoction high-dose group,and the irbesartan treatment group.The normal group was fed with routine feed and intraperitoneal injection of an one-time citric acid buffer.The other 50 animals were fed with high-fat feed and molded with streptozotocin injection.After the successful modeling,Liuwei Dihuang Decoction was given as intragastric treatment,positive control was treated with irbesartan.After the administration,the urine was collected for 24 h and the protein content was detected by biochemical methods.The serum levels of inflammatory factors interleukin-6(IL-6)and interleukin-1β(IL-1β)were measured by ELISA.The rats were weighed,killed,and the renal tissues were separated.Hematoxylin-eosin staining(H&E)was used to observe the changes of renal tissues in each group.The expression level of miR-26a was detected by qPCR.Western blot and immunohistochemistry were used to detect TRPC6 expression in renal tissues.Results:Compared to the normal group,fasting blood glucose,24 h urinary protein,and creatinine levels in the model group were significantly increased,body weight was decreased,renal index was increased,IL-6 and IL-1βexpressions were significantly increased,miR-26a expression was decreased,TRPC6 expression level was increased(P<0.05),and mesonephric tissue damage was severe in the model group.Compared to the model group,after the intragastric administration of Liuwei Dihuang Decoction,fasting blood glucose,24 h urinary protein,and creatinine levels were decreased,body weight was increased,renal index was decreased,IL-6 and IL-1βexpressions were decreased,miR-26a expression was enhanced,TRPC6 expression was inhibited(P<0.05),and renal tissue

关 键 词：糖尿病肾病 六味地黄汤 miR-26a TRPC6 

分 类 号：R285.5[医药卫生—中药学]