南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (11): 1965-1970.doi: 10.12122/j.issn.1673-4254.2023.11.18

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肌肽对糖尿病肾病大鼠肾组织AKT/mTOR通路及自噬的影响

任 毅，卢金莹，于 露，李宗泽，王 高，杨 菁   

  1. 锦州医科大学基础医学院生物化学与分子生物学教研室，辽宁 锦州 121001
  • 出版日期:2023-11-20 发布日期:2023-12-08

Carnosine protects against diabetic nephropathy in rats by activating the AKT/mTOR pathway and restoring autophagy in the renal tissue

REN Yi, LU Jinying, YU Lu, LI Zongzhe, WANG Gao, YANG Jing   

  1. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Jinzhou Medical University, Jinzhou 121001, China
  • Online:2023-11-20 Published:2023-12-08

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摘要： 目的 探究肌肽对糖尿病肾脏病变的保护作用及机制。方法 将70只大鼠随机分成对照组（CON组，n=14）和高糖高脂组（n=56）。CON组普通饲料喂养，高糖高脂组采用高糖高脂喂养，并结合腹腔注射链脲佐菌素建立损伤模型，将制备损伤模型成功的大鼠随机分为糖尿病组（DM组，n=12）及肌肽低（Car-L，n=13）、中（Car-M，n=13）、高剂量组（Car-H，n=13），分别按照0、100、300和900 mg/(kg·d)肌肽灌胃。测量大鼠体质量及血糖，实验结束时收集大鼠24 h尿液、血清及肾脏，分别测量尿量、尿蛋白含量、血肌酐（Scr）、肾脏质量及HE染色，TBA法检测肾脏组织丙二醛（MDA）含量、NBT法检测超氧化物歧化酶（SOD）活性、Western blot法检测肾脏组织中蛋白激酶B（AKT）、p-AKT、哺乳动物雷帕霉素靶蛋白（mTOR）、p-mTOR、微管相关轻链蛋白1轻链3（LC3）、选择性自噬接头蛋白（p62）的表达。结果 与CON组相比，DM组大鼠出现毛色暗淡、毛发潮湿等现象；体质量下降，血糖、尿蛋白含量、24h尿量、Scr、肾脏质量均上升；肾小球肿胀变形，肾小管狭窄；SOD活性下降、MDA含量上升；肾脏组织中p-AKT/AKT和p-mTOR/mTOR比值降低，LC3II/I比值和p62蛋白表达增高（P<0.01）。与DM组相比，肌肽各组的大鼠毛发恢复光泽、体质量回升，血糖、尿蛋白含量、24 h尿量、Scr、肾脏质量有所下降；肾小球肿胀变形、肾小管狭窄程度有所缓解；SOD活性上升、MDA含量下降（P<0.01）；肾脏组织中p-AKT/AKT和p-mTOR/mTOR比值升高、LC3 II/I比值降低、p62蛋白表达降低（P<0.01）。结论 肌肽对糖尿病大鼠肾脏病变具有保护作用，其保护作用与肌肽抑制氧化应激，激活AKT/mTOR通路，进而恢复自噬功能有关。

关键词: 肌肽；糖尿病肾病；自噬；蛋白激酶B；mTOR

Abstract: Objective To explore the mechanisms mediating the protective effect of carnosine against nephropathy in rats with diabetes mellitus (DM). Methods Rat models of DM established by high-fat diet feeding and streptozotocin injection were randomized into DM group and 3 treatment groups with daily carnosine treatment at 100, 300, and 900 mg/kg. Body weight and blood glucose level changes of the rats were measured regularly. After the treatment, 24-h urine, serum samples and kidneys of the rats were collected to measure urine volume, urine protein content, blood creatinine, and kidney mass; renal pathology was observed using HE staining, and MDA content and SOD activity in the kidney tissues were detected. Western blotting was performed to detect the protein expressions of p-AKT, AKT, p-mTOR, mTOR, LC3 and p62 in the kidney tissues. Results Compared with normal control rats, the diabetic rats exhibited dull and wet hair and showed decreased body weight, increased blood glucose, urinary protein content, 24-h urine volume, blood creatinine, and kidney mass with obvious swelling and deformation of the glomeruli, narrowing of the renal tubules, decreased SOD activity and increased MDA content, lowered p-mTOR/mTOR and p-AKT/AKT ratios and increased LC3 II/I ratio and p62 protein expression in the kidney tissue. The diabetic rats receiving carnosine treatments had dry hair with normal luster and showed increased body weight and slightly decreased blood glucose, urinary protein content, 24-h urine volume, blood creatinine, and kidney mass. The treatment also improved renal pathology, increased SOD activity, decreased MDA content, increased p-mTOR/mTOR and p-AKT/AKT ratios and lowered LC3 II/I ratio and p62 protein expression in renal tissue of the diabetic rats. Conclusion Carnosine offers protection against nephropathy in rats with DM possibly by inhibiting oxidative stress, activating the AKT/mTOR pathway, and restoring autophagy in the kidneys.

Key words: carnosine; diabetic kidney disease; autophagy; AKT; mTOR