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

ZHANG Shuai; LI Jiao; WANG Xingbing; WEN Yingjuan

Abstract：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-α subunit 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-1α in 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-1α in 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-1α in 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 expression of AMPK,SIRT1 and PGC-1α,restoring the skeletal muscle MMP levels.At the same time,by reducing the serum AChR-ab level,the damage of AchR at the neuromuscular junction can be alleviated and the muscle fiber morphology of skeletal muscle can be improved.