Effects of Huangqi Decoction on mitochondrial damage of skeletal muscle cells in rats with sarcopenia secondary to chronic cholestasis
Objective:To explore the pathogenic mechanism of sarcopenia secondary to chronic cholestasis and the regulatory effect of Huangqi Decoction based on skeletal muscle cell mitochondrial damage.Methods:Forty male Wistar rats were randomly divided into normal group,model group,low-dose Huangqi Decoction group and high-dose Huangqi Decoction group,with 10 rats in each group.Except for the normal group,the other groups were given α-naphthalene isothiocyanate-olive oil solution once every other day for 40 weeks to induce the rat model of chronic cholestatic liver disease complicated with sarcopenia.The low and high-dose(0.59,1.76 g/kg)of Huangqi Decoction were given on the first day of the 33rd week,once a day for 8 consecutive weeks and ended at the end of the 40th week.The peripheral blood,liver and skeletal muscle tissue were collected.The muscle mass and strength were recorded.The histopathological changes of liver and skeletal muscle tissue were observed by HE and Sirius red staining.Transmission electron microscopy was used to observe the ultrastructural and morphological changes of mitochondria in skeletal muscle cells.The serum liver function indexes were detected by routine biochemical methods.JC-1 probe was used to detect mitochondrial membrane potential in skeletal muscle cells.Detection of ATP concentration in skeletal muscle tissue by bioluminescence.The expression of MAFbx/Atrogin-1,MuRF1,LC3B,PINK1,Bnip3 and UCP2 in skeletal muscle tissue were detected by Western Blot.Results:The muscle mass,muscle strength,histopathology of liver and skeletal muscle tissue,mitochondrial ultrastructure of skeletal muscle cells,serum liver function indexes,mitochondrial membrane potential and mitochondrial ATP content of skeletal muscle cell,and the expression of MAFbx/Atrogin-l,MuRFl,LC3B,PINK1,Bnip3 and UCP2 protein in skeletal muscle tissue were significantly changed in the model group(P＜0.01).Both low-dose and high-dose Huangqi Decoction could significantly improve the muscle strength,histopathology of liver and skeletal muscle tissue,mitochondrial ultrastructure of skeletal muscle cells,serum liver function indexes,mitochondrial membrane potential and mitochondrial ATP content of skeletal muscle cell,and the expression of MAFbx/Atrogin-1,MuRF1,LC3B,PINK1,Bnip3 and UCP2 protein in skeletal muscle tissue(P＜0.05,P＜0.01).Conclusion:The disturbance of mitochondrial energy synthesis,excessive mitochondrial autophagy and the increase of skeletal muscle protein decomposition in skeletal muscle cells may be one of the main pathological mechanisms of sarcopenia secondary to chronic cholestasis.Huangqi Decoction can reduce the breakdown of skeletal muscle protein by improving mitochondrial energy synthesis and mitochondrial autophagy in skeletal muscle cells,thereby preventing skeletal muscle atrophy,improving muscle strength,and playing a role in the prevention and treatment of sarcopenia secondary to chronic cholestasis.
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