从线粒体能量代谢探讨葛根复方对重症肌无力模型大鼠的机制研究  

Study on the Mechanism of Gegen Compound in Myasthenia Gravis Model Rats from the Perspective of Mitochondrial Energy

作　　者：张帅[1] 李娇 王兴兵 文颖娟[1] ZHANG Shuai;LI Jiao;WANG Xingbing;WEN Yingjuan(Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046

出　　处：《中国中医基础医学杂志》2025年第2期280-286,共7页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金项目(81202642);陕西省重点研发计划一般项目(S2023-YF-YBSF-0969)。

摘　　要：目的观察葛根复方对实验性自身免疫性重症肌无力(experimental autoimmune myasthenia gravis,EAMG)大鼠骨骼肌线粒体能量代谢的影响,并探讨其作用机制。方法将42只SD大鼠随机分为空白组,模型组,强的松组,葛根复方高、中、低剂量组,每组7只。除空白组外,余5组大鼠均采用含有鼠源性AChR-α亚基R97~R116肽段的免疫乳剂皮下多点注射制备EAMG大鼠模型。治疗前后记录各组大鼠体质量和Lennon评分,灌胃治疗4周后,采用ELISA法检测血清乙酰胆碱受体抗体(AChR-ab)水平,HE染色观察骨骼肌形态变化,试剂盒检测骨骼肌线粒体膜电位水平,Western blot检测骨骼肌腺苷酸活化蛋白激酶(AMPK)、沉默信息调节因子1(SIRT1)、过氧化物酶体增殖物激活受体γ辅激活因子-1α(PGC-1α)蛋白表达量。结果与空白组比较,模型组大鼠体质量下降,肌无力症状明显,血清AChR-ab水平升高(P<0.01),病理结果显示骨骼肌肌纤维萎缩,伴有结缔组织形成及炎性细胞浸润,线粒体膜电位水平与骨骼肌AMPK、SIRT1、PGC-1α蛋白表达均降低(P<0.01)。治疗后,与模型组比较,各给药组大鼠体质量升高,肌无力症状改善,血清AChR-ab水平降低(P<0.01),骨骼肌肌纤维萎缩和炎性浸润改善,线粒体膜电位水平上升(P<0.01),骨骼肌AMPK和SIRT1、PGC-1α蛋白表达均升高(P<0.05)。结论葛根复方通过提高EAMG大鼠AMPK、SIRT1、PGC-1α蛋白表达,恢复骨骼肌线粒体膜电位水平,从而改善大鼠线粒体能量代谢功能,缓解肌无力;同时通过降低血清AChR-ab水平,减轻神经肌肉接头处AchR的损害,改善骨骼肌肌纤维形态。Objective To study the effect of Gegen compound on energy metabolism of skeletal muscle mitochondria in experimental autoimmune myasthenia gravis(EAMG)rats and discuss its mechanism.Methods 42 rats were randomly divided into blank group,model group,western medicine group,Gegen compound low group,Gegen compound medium group,and Gegen compound high group.Except for the blank group,the remaining 5 groups of rats were prepared with EAMG rat models by subcutaneous multi-point injection of immune emulsion containing mouse derived AChR-αsubunit R97-R116 peptides.The body mass and Lennon score of rats in each group were recorded before and after treatment.After 4 weeks of gavage treatment,the concentration of AChR-ab was detected by ELISA,and the pathological changes of skeletal muscle were observed by HE staining.Then an assay kit was used to detect the mitochondrial membrane potential(MMP)of skeletal muscle.Finally,the protein expression levels of AMPK,SIRT1 and PGC-1αin skeletal muscle of rats were detected by Western blot.Results Compared with the blank group,the body mass of the rats in the model group decreased,the symptoms of muscle weakness were obvious,and the serum AChR-ab level increased(P<0.01),pathological findings showed atrophy of skeletal muscle fibers accompanied by connective tissue formation and inflammatory cell infiltration,the level of MMP and the protein expressions of AMPK,SIRT1 and PGC-1αin skeletal muscle were decreased(P<0.01)in the model group.After treatment,compared with the model group,the body mass of the rats in each treatment group increased and the symptoms of muscle weakness improved,the serum AChR-ab level decreased(P<0.01),the muscle fiber atrophy and inflammatory infiltration improved,and the level of MMP increased(P<0.01).The protein expressions of AMPK,SIRT1 and PGC-1αin skeletal muscle were increased in each treatment group(P<0.01).Conclusion Gegen compound can improve the function of mitochondrial energy metabolism and relieve muscle weakness in EAMG rats by increasing the e

关 键 词：重症肌无力 葛根复方 骨骼肌 线粒体膜电位 线粒体能量代谢 

分 类 号：R285[医药卫生—中药学]