自噬抑制剂 3-甲基腺嘌呤可减轻链脲佐菌素诱导的糖尿病小鼠的肾损伤。

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Haiwen Ren, Mengxin Huang, Liwen Ou, Xuan Deng, Xin Wu, Quan Gong, Benju Liu
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引用次数: 0

摘要

目的研究 3-甲基腺嘌呤(3-MA)能否保护链脲佐菌素(STZ)诱导的糖尿病小鼠的肾脏,并探讨其可能的机制:用 STZ 诱导 C57BL/6J 小鼠患糖尿病。将小鼠分为正常对照组(NC)、糖尿病组(DM)和糖尿病+3-MA干预组(DM+3-MA)。每周记录血糖、饮水量和体重。药物治疗第 6 周结束时,收集 24 小时尿液。收集血液和肾脏进行 PAS 染色,以评估肾脏损伤程度。天狼星红染色用于评估胶原沉积。血尿素氮(BUN)、血清肌酐和 24 小时尿白蛋白用于评估肾功能。用 Western 印迹法检测纤维化相关蛋白、炎症介质、高迁移率基团框 1(HMGB1)/NF-κB 信号通路分子、血管内皮生长因子(VEGF)和荚膜蛋白,用免疫组化法(IHC)检测自噬相关蛋白和纤维连接蛋白的表达和定位:结果:与正常对照组小鼠的肾脏相比,糖尿病对照组小鼠的肾脏更加苍白和肥大。高血糖诱导肾脏自噬,激活 HMGB1/NF-κB 信号通路,导致肾脏炎症介质、细胞外基质(ECM)沉积和蛋白尿增加。结论:3-MA 可通过抑制自噬和 HMGB1/NF-κB 信号通路,减轻 STZ 诱导的糖尿病小鼠的肾损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Autophagy inhibitor 3-methyladenine attenuates renal injury in streptozotocin-induced diabetic mice.

Objectives: To investigate whether 3-methyladenine (3-MA) can protect the kidney of streptozotocin (STZ) - induced diabetes mice, and explore its possible mechanism.

Materials and methods: STZ was used to induce diabetes in C57BL/6J mice. The mice were divided into normal control group (NC), diabetes group (DM), and diabetes+3-MA intervention group (DM+3-MA). Blood glucose, water consumption, and body weight were recorded weekly. At the end of the 6th week of drug treatment, 24-hour urine was collected. Blood and kidneys were collected for PAS staining to evaluate the degree of renal injury. Sirius red staining was used to assess collagen deposition. Blood urea nitrogen (BUN), serum creatinine, and 24-hour urine albumin were used to evaluate renal function. Western blot was used to detect fibrosis-related protein, inflammatory mediators, high mobility group box 1 (HMGB1)/NF-κB signal pathway molecule, vascular endothelial growth factor (VEGF), and podocin, and immunohistochemistry (IHC) was used to detect the expression and localization of autophagy-related protein and fibronectin.

Results: Compared with the kidney of normal control mice, the kidney of diabetes control mice was more pale and hypertrophic. Hyperglycemia induces renal autophagy and activates the HMGB1/NF-κB signal pathway, leading to the increase of inflammatory mediators, extracellular matrix (ECM) deposition, and proteinuria in the kidney. In diabetic mice treated with 3-MA, blood glucose decreased, autophagy and HMGB1/NF-κB signaling pathways in the kidneys were inhibited, and proteinuria, renal hypertrophy, inflammation, and fibrosis were improved.

Conclusion: 3-MA can attenuate renal injury in STZ-induced diabetic mice through inhibition of autophagy and HMGB1/NF-κB signaling pathway.

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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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