基于Connexin 43自噬环路研究参芪复方保护糖尿病肾病足细胞的作用机制

批准号:
82004351
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
唐诗韵
依托单位:
学科分类:
中医内科学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
唐诗韵
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中文摘要
以“养阴益气活血”为治法的参芪复方治疗糖尿病肾病临床疗效确切,但作用机制不清。前期研究发现,参芪复方对糖尿病肾病肾小球足细胞具有保护作用,其机理与维持足细胞自噬通量密切相关。最新研究发现,Connexin 43(Cx 43)自噬环路在足细胞损伤过程中起到关键作用。本项目据此提出假说:参芪复方可通过调控Cx 43自噬环路,改善足细胞自噬通量,发挥保护足细胞的作用。本项目研究采用db/db小鼠模型,同时采用siRNA沉默Cx 43作为验证对照,在体探寻和验证参芪复方的作用规律和作用靶点;采用MPC5细胞高糖环境构建损伤模型,同时采用siRNA沉默Cx 43表达,氯喹抑制自噬小体融合,雷帕霉素诱导自噬作为验证对照,从细胞层面验证参芪复方干预Cx 43自噬环路的作用靶点。项目研究结果对揭示参芪复方治疗糖尿病肾病的作用机制,阐明“养阴益气活血”治法的科学内涵具有重要意义。
英文摘要
Shenqi compound prescription is the representative of "Nourishing Yin, nourishing qi and promoting blood circulation" therapy. Shenqi compound prescription has a definite clinical effect on diabetic nephropathy, but its mechanism is unclear. It was found that Shenqi compound prescription has protective effect on podocytes of diabetic nephropathy, and its mechanism is closely related to maintaining the autophagy flux in podocytes. Recently, it has been found that connexin 43 autophagy loop plays a key role in podocyte damage. So we hypothesized that Shenqi compound prescription can regulate connexin 43 autophagy loop, improve the autophagy flux of podocytes, and play the role of protecting podocytes. In this study, db/db mouse model was used, and the expression of connexin 43 silenced by siRNA was used as the verification control to explore and verify the action rule and target of Shenqi compound in the treatment of diabetic nephropathy in vivo; In vitro, MPC5 cell in high glucose environment was used to build the damage model, at the same time, connexin 43 silenced by siRNA 43 expression, chloroquine inhibited the fusion of autophagy, and rapamycin induced autophagy was used as the verification control, from the cell level to verify the intervention target of Shenqi compound prescription on connexin 43 autophagy loop. The results of the project are of great significance to reveal the mechanism of Shenqi compound prescription in the treatment of diabetic nephropathy and to clarify the scientific connotation of the treatment method of "Nourishing Yin, supplementing qi and activating blood circulation".
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DOI:--
发表时间:2023
期刊:成都医学院学报
影响因子:--
作者:罗文婷;唐诗韵;肖湘;罗斯敏;杨子璇;黄巍;唐宋琪
通讯作者:唐宋琪
DOI:10.2147/dmso.s408170
发表时间:2023
期刊:Diabetes, metabolic syndrome and obesity : targets and therapy
影响因子:--
作者:
通讯作者:
DOI:10.1016/j.biopha.2023.116039
发表时间:2024
期刊:Biomedicine Pharmacotherapy
影响因子:--
作者:Li Song;Wei Zhang;Shi-yun Tang;Si-min Luo;Pei-yu Xiong;Jun-yu Liu;Heng-chang Hu;Ying-qi Chen;Bo Jia;Qian-hua Yan;Song-qi Tang;Wei Huang
通讯作者:Wei Huang
国内基金
海外基金
