南方医科大学学报

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (1): 94-103.doi: 10.12122/j.issn.1673-4254.2026.01.10

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清解扶正颗粒通过抑制线粒体依赖的凋亡、激活AMPK-PGC-1α通路缓解5-氟尿嘧啶引起的骨骼肌损伤

赵锦燕1,2,3(), 彭娇1, 林明和1, 朱晓勤1,2,3, 黄彬1,2,3, 林久茂1,2,3()   

  1. 1.福建中医药大学，中西医结合学院，福建 福州 350122
    2.福建中医药大学，中西医结合研究院，福建 福州 350122
    3.福建中医药大学，福建省中西医结合老年性疾病重点实验室，福建 福州 350122
  • 收稿日期:2025-05-17 出版日期:2026-01-20 发布日期:2026-01-16
  • 通讯作者: 林久茂 E-mail:zhaojinyan0928@163.com;linjiumao@fjtcm.edu.cn
  • 作者简介:赵锦燕，博士，副研究员，E-mail: zhaojinyan0928@163.com
  • 基金资助:
    国家自然科学基金(81303125);福建省自然科学基金(2021J01939);福建省自然科学基金(2022J01368)

Qingjie Fuzheng Granules alleviates 5-fluorouracil-induced skeletal muscle injury in tumor-bearing mice by inhibiting mitochondria-dependent apoptosis and activating the AMPK-PGC-1α pathway

Jinyan ZHAO1,2,3(), Jiao PENG1, Minghe LIN1, Xiaoqin ZHU1,2,3, Bin HUANG1,2,3, Jiumao LIN1,2,3()   

  1. 1.College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
    2.Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
    3.Fujian Provincial Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
  • Received:2025-05-17 Online:2026-01-20 Published:2026-01-16
  • Contact: Jiumao LIN E-mail:zhaojinyan0928@163.com;linjiumao@fjtcm.edu.cn
  • Supported by:
    National Natural Science Foundation of China(81303125)

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摘要：

目的 探讨清解扶正颗粒（QFG）缓解5-氟尿嘧啶（5-FU）导致骨骼肌萎缩的作用及其机制。 方法 采用CT26细胞制备小鼠皮下移植瘤模型，10只/组，待瘤体长至100 mm3，根据瘤体大小将小鼠分为对照（CT26）组、模型（5-FU，50 mg/kg）组、干预（5-FU，50 mg/kg+QFG，1 g/kg）组，同时设置正常组。模型组和干预组小鼠给予5-FU腹腔注射，1次/3 d；干预组同时灌胃 QFG，1次/d；正常组和对照组小鼠腹腔注射和灌胃等体积的生理盐水，连续干预21 d。在干预前1 d以及干预第20天进行抓力试验和悬挂试验；在第21天取材后称量瘤体质量和腓肠肌的质量；苏木素-伊红（HE）染色、透射电镜和原位末端转移酶标记（TUNEL）法观察腓肠肌组织形态改变；比色法检测腓肠肌三磷酸腺苷酶（ATP）含量；免疫组织化学（IHC）方法检测腓肠肌AMPK、PGC-1α、细胞色素（Cyto）C、凋亡诱导因子（AIF）、凋亡蛋白酶激活因子（Apaf）-1、第二个线粒体衍生半胱天冬氨酸蛋白酶激活剂（Smac）、B细胞淋巴瘤（Bcl）-2、Bcl-2相关X蛋白（Bax）和剪切的天冬氨酸特异性半胱氨酸蛋白酶（cleaved caspase-3）和cleaved caspase-9蛋白表达。 结果 与正常组比较，对照组腓肠肌质量、抓力和悬挂评分变小（P<0.05），腓肠肌纤维结构和超微结构损伤，线粒体减少，ATP含量降低（P<0.05），细胞凋亡率增加（P<0.05），腓肠肌AMPK、PGC-1α、Bcl-2表达降低（均P<0.05），Bax、Cyto C、AIF、Apaf-1、Smac、cleaved caspase-3 和cleaved caspase-9表达升高（均P<0.05）。与对照组比较，模型组腓肠肌质量、抓力和悬挂评分更小（P<0.05），腓肠肌纤维结构和超微结构损伤严重，ATP含量降低（P<0.05），细胞凋亡进一步增加（P<0.05），腓肠肌AMPK、PGC-1α、Bcl-2表达降低（均P<0.05），Bax、Cyto C、AIF、Apaf-1、Smac、cleaved caspase-3 和cleaved caspase-9 表达升高（均P<0.05）。与模型组比较，干预组腓肠肌质量、抓力和悬挂评分增加（均P<0.015），腓肠肌纤维结构和超微结构损伤减轻，细胞凋亡减少（P<0.05），腓肠肌AMPK、PGC-1α、Bcl-2表达升高（均P<0.05），Bax、Cyto C、AIF、Apaf-1、Smac、cleaved caspase-3 和cleaved caspase-9表达降低（均P<0.05）。 结论 QFG缓解5-FU所致荷瘤小鼠的骨骼肌疲劳，其机制与AMPK/PGC-1α通路活化，抑制腓肠肌线粒体依赖性细胞凋亡有关。

关键词: 清解扶正颗粒, 腺苷酸活化蛋白激酶, 过氧化物酶体增殖物受体γ共激活因子-1α, 线粒体生成, 骨骼肌凋亡

Abstract:

Objective To explore the therapeutic mechanism of Qingjie Fuzheng granules (QFG) for alleviating 5-fluorouracil (5-FU)-induced skeletal muscle atrophy. Methods Male BALB/c mice bearing subcutaneous colorectal cancer CT26 cell xenografts were randomized into control group, model group, and treatment group. The mice in model and treatment groups were given intraperitoneal 5-FU injections every 3 days and treated with daily gavage of saline and QFG for 21 days, respectively; the mice in the control group and normally fed mice were given only saline gavage. Gripping test and hanging test of the mice were performed before and after the treatment, and on day 21, tumor weight and gastrocnemius muscle weight were measured, and histopathology and cell apoptosis in the gastrocnemius muscle were examined with HE staining, transmission electron microscopy and TUNEL assay. ATP content in the muscle was measured, and protein expressions of AMPK, PGC-1α, Cyt c, AIF, Apaf-1, Smac, Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 were determined with immunohistochemistry. Results The tumor-bearing mice in the control group showed significantly decreased gastrocnemius muscle weight and grip and suspension test scores. The gastrocnemius muscle showed ultrastructure injuries with lowered ATP content, obvious cell apoptosis, decreased expressions of AMPK, PGC-1 α, and Bcl-2, and increased expressions of Bax, Cyto C, AIF, Apaf-1, Smac, cleaved caspase-3 and cleaved caspase-9. These changes were obviously worsened in 5-FU-treated mice, while QFG treatment significantly increased gastrocnemius muscle weight and strength, ameliorated its ultrastructural injuries, reduced cell apoptosis, and reversed the abnormal protein expressions. Conclusion QFG alleviates 5-FU-induced skeletal muscle fatigue in tumor-bearing mice by activating the AMPK/PGC-1α pathway and inhibiting mitochondria-dependent apoptosis in the gastrocnemius muscle.

Key words: Qingjiefuzheng granule, AMP-activated protein kinase, peroxisome proliferator-activated receptor γ coactivator-1α, mitochondrial biogenesis, skeletal muscle apoptosis