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津力达颗粒通过AMPK/PGC-1α途径减轻糖尿病肾病中的足细胞凋亡和线粒体功能障碍。

Jinlida granules alleviate podocyte apoptosis and mitochondrial dysfunction via the AMPK/PGC‑1α pathway in diabetic nephropathy.

作者信息

Sun Shengnan, Yang Shurong, Cheng Ying, Fang Ting, Qu Jingru, Tian Lei, Zhang Man, Wu Shi, Sun Bei, Chen Liming

机构信息

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien‑I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, P.R. China.

出版信息

Int J Mol Med. 2025 Feb;55(2). doi: 10.3892/ijmm.2024.5467. Epub 2024 Dec 13.

Abstract

Traditional Chinese Medicine (TCM) has demonstrated promising efficacy in managing and preventing the early‑stage diabetic nephropathy (DN). Although the exact mechanisms remain elusive, clinical evidence has suggested that Jinlida granules (JLD) are beneficial in improving renal function among patients with DN. The present study aimed to elucidate the effect of JLD on DN and the underlying molecular mechanism. Therefore, podocyte apoptosis was evaluated using flow cytometry and TUNEL staining, while mitochondrial morphology and function were assessed using transmission electron microscopy, MitoTracker, JC‑1 and reactive oxygen species staining. RNA sequencing analysis was performed to elucidate the mechanism underlying the effect of JLD on DN. Additionally, to investigate the role of peroxisome proliferator‑activated receptor‑γ co‑activator‑1α (PGC‑1α) in mitigating JLD‑induced mitochondrial dysfunction and podocyte apoptosis, MPC5 cells were transfected with the corresponding small interfering RNA constructs. The results showed that JLD effectively improved renal function and mitigated podocyte injury, as well as ameliorated mitochondrial dysfunction and inhibited apoptosis in db/db mice. experiments further revealed that JLD exerted a protective effect via inhibiting mitochondrial fission and apoptosis in high glucose‑treated podocytes. Furthermore, JLD enhanced the phosphorylation of adenosine monophosphate‑activated protein kinase (AMPK), thus promoting the expression of PGC‑1α, eventually improving apoptosis and mitochondrial homeostasis. Overall, the current study revealed that JLD could improve mitochondrial homeostasis and reduce cell apoptosis in podocytes via activating the AMPK/PGC‑1α pathway, thus providing a theoretical foundation for the clinical management of DN.

摘要

传统中医(TCM)在管理和预防早期糖尿病肾病(DN)方面已显示出有前景的疗效。尽管确切机制仍不清楚,但临床证据表明,津力达颗粒(JLD)对改善DN患者的肾功能有益。本研究旨在阐明JLD对DN的作用及其潜在的分子机制。因此,使用流式细胞术和TUNEL染色评估足细胞凋亡,同时使用透射电子显微镜、MitoTracker、JC-1和活性氧染色评估线粒体形态和功能。进行RNA测序分析以阐明JLD对DN作用的潜在机制。此外,为了研究过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)在减轻JLD诱导的线粒体功能障碍和足细胞凋亡中的作用,用相应的小干扰RNA构建体转染MPC5细胞。结果表明,JLD有效改善了db/db小鼠的肾功能,减轻了足细胞损伤,改善了线粒体功能障碍并抑制了细胞凋亡。实验进一步表明,JLD通过抑制高糖处理的足细胞中的线粒体分裂和凋亡发挥保护作用。此外,JLD增强了单磷酸腺苷激活蛋白激酶(AMPK)的磷酸化,从而促进了PGC-1α的表达,最终改善了细胞凋亡和线粒体稳态。总体而言,当前研究表明,JLD可通过激活AMPK/PGC-1α途径改善线粒体稳态并减少足细胞凋亡,从而为DN的临床管理提供理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf4a/11670860/a08a37f99b56/ijmm-55-02-05467-g00.jpg

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