人参皂苷Rg1通过靶向mTOR/NF-κB/NLRP3轴减轻高脂血症诱导的足细胞损伤。
Ginsenoside Rg1 Alleviates Podocyte Injury Induced by Hyperlipidemia via Targeting the mTOR/NF-B/NLRP3 Axis.
作者信息
Wang Tao, Gao Yanbin, Yue Rongchuan, Wang Xiaolei, Shi Yimin, Xu Jiayi, Wu Bingjie, Li Yimeng
机构信息
School of Traditional Chinese Medicine, Capital Medical University, 10 Youanmenwai, Xitoutiao, Fengtai District, Beijing, China.
School of North Sichuan Medical College, Nanchong 637000, China.
出版信息
Evid Based Complement Alternat Med. 2020 Oct 9;2020:2735714. doi: 10.1155/2020/2735714. eCollection 2020.
BACKGROUND
Podocyte injury plays an important role in diabetic nephropathy (DN). The aim of this study was to determine the potential therapeutic effects of the ginsenoside Rg1 on hyperlipidemia-stressed podocytes and elucidate the underlying mechanisms.
METHODS
and models of DN were established as previously described, and the expression levels of relevant markers were analyzed by Western blotting, real-time Polymerase Chain Reaction (PCR), immunofluorescence, and immunohistochemistry.
RESULTS
Ginsenoside Rg1 alleviated pyroptosis in podocytes cultured under hyperlipidemic conditions, as well as in the renal tissues of diabetic rats, and downregulated the mammalian target of rapamycin (mTOR)/NF-B pathway. In addition, Rg1 also inhibited hyperlipidemia-induced NLRP3 inflammasome in the podocytes, which was abrogated by the mTOR activator L-leucine (LEU). The antipyroptotic effects of Rg1 manifested as improved renal function in the DN rats.
CONCLUSION
Ginsenoside Rg1 protects podocytes from hyperlipidemia-induced damage by inhibiting pyroptosis through the mTOR/NF-B/NLRP3 axis, indicating a potential therapeutic function in DN.
背景
足细胞损伤在糖尿病肾病（DN）中起重要作用。本研究旨在确定人参皂苷Rg1对高脂血症应激足细胞的潜在治疗作用，并阐明其潜在机制。
方法
按照先前描述建立DN模型，通过蛋白质免疫印迹法、实时聚合酶链反应（PCR）、免疫荧光和免疫组织化学分析相关标志物的表达水平。
结果
人参皂苷Rg1减轻了高脂血症条件下培养的足细胞以及糖尿病大鼠肾组织中的细胞焦亡，并下调了雷帕霉素靶蛋白（mTOR）/核因子-κB（NF-κB）信号通路。此外，Rg1还抑制了高脂血症诱导的足细胞中NLRP3炎性小体，而mTOR激活剂L-亮氨酸（LEU）可消除这种抑制作用。Rg1的抗细胞焦亡作用表现为DN大鼠肾功能的改善。
结论
人参皂苷Rg1通过mTOR/NF-κB/NLRP3轴抑制细胞焦亡，保护足细胞免受高脂血症诱导的损伤，表明其在DN中具有潜在的治疗作用。
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