Sinomenine Hydrochloride Activates Podocyte Autophagy by Attenuating PI3K/AKT/mTOR Pathways to Protect Diabetic Nephropathy

IF 2.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lihan Xie, Weinan Li, Shiqi Fan, Jinsong Jin
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Abstract

Diabetic kidney disease (DKD) is a common complication of diabetes, often characterized by podocyte injury, proteinuria, and eventual renal failure. Sinomenine hydrochloride (SH), an active component derived from traditional Chinese medicine, is clinically effective in treating kidney diseases. This study investigates the protective effects of SH on podocytes under high-glucose conditions and its mechanism of action. Mouse podocytes (MPC-5) were treated with SH at concentrations of 50, 200, and 600 μg/mL under high-glucose conditions (30 mmol/L) for 24 h to establish a DKD model. Cell viability was assessed using CCK-8 assays, and apoptosis rates were measured using flow cytometry. Autophagy levels were evaluated by detecting LC3-II, Beclin-1, and P62 proteins via Western blot analysis, while the involvement of the PI3K/AKT/mTOR pathway was analyzed by examining phosphorylated AKT and mTOR. Transmission electron microscopy was employed to observe autophagosomes. SH improved podocyte viability, reduced apoptosis, and enhanced autophagic activity by increasing LC3-II and Beclin-1 expression while decreasing P62 levels. SH also downregulated p-AKT and p-mTOR, indicating inhibition of the PI3K/AKT/mTOR pathway. Electron microscopy confirmed increased autophagosomes in SH-treated groups. SH protects podocytes in a high-glucose environment by enhancing autophagy through inhibition of the PI3K/AKT/mTOR pathway. These findings provide insights into SH as a potential therapeutic agent for DKD management.

Abstract Image

盐酸青藤碱通过抑制PI3K/AKT/mTOR通路激活足细胞自噬保护糖尿病肾病
糖尿病肾病(DKD)是糖尿病的常见并发症,通常以足细胞损伤、蛋白尿和最终的肾功能衰竭为特征。盐酸青藤碱(SH)是一种从中药中提取的有效成分,在临床上具有治疗肾脏疾病的疗效。本研究探讨了SH在高糖条件下对足细胞的保护作用及其作用机制。在高糖(30 mmol/L)条件下,分别以50、200、600 μg/mL的SH作用小鼠足细胞(MPC-5) 24 h,建立DKD模型。CCK-8检测细胞活力,流式细胞术检测细胞凋亡率。通过Western blot检测LC3-II、Beclin-1和P62蛋白来评估自噬水平,通过检测磷酸化的AKT和mTOR来分析PI3K/AKT/mTOR通路的参与情况。透射电镜观察自噬体。SH通过增加LC3-II和Beclin-1表达,降低P62水平,提高足细胞活力,减少凋亡,增强自噬活性。SH还下调了p-AKT和p-mTOR,表明PI3K/AKT/mTOR通路受到抑制。电镜检查证实sh处理组自噬体增加。SH通过抑制PI3K/AKT/mTOR通路增强自噬,从而在高糖环境中保护足细胞。这些发现为SH作为DKD管理的潜在治疗剂提供了见解。
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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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