基于AMPK/SIRT1/PGC-1α信号通路探讨补中益气汤对5-FU诱导的肌少症的调节作用OA
Investigating the regulatory effect of Buzhong Yiqi Decoction on sacopenia induced by 5-FU via AMPK/SIRT1/PGC-1α signaling pathway
目的:探讨补中益气汤通过调控AMPK/SIRT1/PGC-1α信号通路对化疗药物5-FU诱导的肌少症的改善机制.方法:35只雄性 SD大鼠随机分为 5组(空白对照组、模型组及补中益气汤低、中、高剂量组),每组7只.给药组大鼠分别灌胃不同剂量补中益气汤,连续干预15 d,记录体质量、抓力、力竭游泳时间等生理指标.末次给药后取腓肠肌,进行H&E染色、IHC、ELISA、RT-qPCR和Western blot检测.结果:与空白对照组相比,模型组大鼠体质量、抓力和力竭游泳时间明显降低(P<0.01),腓肠肌组织病理学改变明显,AMP/ATP 比值升高,Atrogin-1 和 MuRF-1 表达上调(P<0.01),MyoD 和 Myogenin 表达下调(P<0.01),p-AMPK/AMPK、SIRT1、PGC-1α蛋白表达降低(P<0.01).补中益气汤各剂量组大鼠上述指标均有所改善,其中中剂量组效果最为明显.结论:补中益气汤对化疗药物5-FU诱导的肌少症具有明显改善作用,其机制可能与激活AMPK/SIRT1/PGC-1α信号通路有关.
Objective:To investigate the effect of Buzhong Yiqi Decoction on chemotherapy drug 5-FU-induced sarcopenia by regulating AMPK/SIRT1/PGC-1α signaling pathway.Methods:A total of thirty-five male SD rats were randomly divided into 5 groups(the control group,the model group,the low,medium and high dose Buzhong Yiqi Decoction groups),with 7 rats in each group.The rats in the administration group were treated with different doses of Buzhong Yiqi Decoction for 15 consecutive days.The body weight,grip strength,exhaustive swimming time and other physiological indexes were recorded.After the last adminis-tration,gastrocnemius muscles were harvested for H&E staining,IHC,ELISA,RT-qPCR,and Western blot.Results:Com-pared to the blank control group,the body weight,grip strength and exhaustive swimming time of the model group were signifi-cantly decreased(P<0.01),the AMP/ATP ratio was increased,the expression of Atrogin-1 and MuRF-1 was up-regulated(P<0.01),and the expression of MyoD and Myogenin was down-regulated(P<0.01).The protein expressions of p-AMPK/AMPK,SIRT1 and PGC-1α were significantly decreased(P<0.01).Buzhong Yiqi Decoction improved the above indexes in rats of each dose group,and the medium-dose group had the most significant effect.Conclusion:Buzhong Yiqi Decoction can significantly im-prove chemotherapy drug 5-FU-induced sarcopenia,and its mechanism may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway.
王艺;张月宇;马贤德;张思琦;雷萍
辽宁中医药大学基础医学院,辽宁 沈阳 110847辽宁中医药大学基础医学院,辽宁 沈阳 110847辽宁中医药大学中医药创新工程技术中心,辽宁 沈阳 110847辽宁中医药大学基础医学院,辽宁 沈阳 110847辽宁中医药大学基础医学院,辽宁 沈阳 110847
医药卫生
化疗肌少症补中益气汤骨骼肌AMPK/SIRT1/PGC-1α信号通路
ChemotherapySarcopeniaBuzhong Yiqi DecoctionSkeletal muscleAMPK/SIRT1/PGC-1α signaling path-way
《海南医科大学学报》 2026 (9)
677-686,10
This study was supported by National Natural Science Foundation of China(82374375)Natural Science Foundation Project of Liaoning Provincial Science and Technology Department(2019-ZD-0444)"Qi Ji Project"of the Integrated Traditional Chinese and Western Medicine College of Liaoning University of Traditional Chinese Medicine 国家自然科学基金(82374375)辽宁省科技厅自然基金计划指导项目(2019-ZD-0444)辽宁中医药大学中西医结合学院"岐济工程"项目
评论