To explore the regulatory effect of Guipi Decoction on chemotherapy-related sarcopenia based on IGF-1/PI3K/Akt/mTOR signaling pathway
Objective To investigate whether the pathogenesis of 5-fluorouracil(5-FU)-induced sarcopenia is related to the insu-lin-like growth factor-1(IGF-1)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway,which is regulated by Guipi Decoction.Methods Forty SPF male SD rats were randomly divided into blank group,model group(28mg/kg5-FU),Guipi Decoction low-dose group(28mg/kg5-FU+0.5g/ml Guipi decoction),medium-dose group(28mg/kg5-FU+1g/ml Guipi decoction)and high-dose group(28mg/kg5-FU+2g/m)1 Guipi Decoction),8 animals in each group.At the same time,Guipi decoction group was given different doses of Guipi decoction,and the intervention lasted for 14 days.After the last administration,the rats were deprived of water and fasted,and the rats were killed the next day,and the gastrecne-mius muscles were taken for detection,during which the physiological status of the rats such as body weight and grasping power were re-corded.The pathological changes of gastrocnemius were observed by hematoxylin-eosin(HE)staining.The expression of muscular at-rophy related proteins Fbxo32 and Trim63 in gastrocnemius was detected by immunohistochemistry(IHC).The contents of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-1 receptor(IGF-1R)in gastrocnemius were detected by enzyme-linked immunosorbent assay(ELISA).Real-time fluorescence quantitative PCR(RT-PCR)was used to determine the mRNA expression lev-els of IGF-1 and IGF-1R in gastrocnemius.Protein expression levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR and mTOR in gas-trocnemius were detected by Western blot.Results Compared with blank group,the body weight and grip strength of rats in model group were significantly decreased(P＜0.01).The myocyte space was enlarged,the nuclei were disordered and the inflammatory cells were infiltrated.The expression levels of IGF-1 and IGF-1R protein and mRNA were increased(P＜0.01);The expressions of Fbxo32 and Trim63 were significantly increased(P＜0.01).The ratios of P-PI3K/PI3K,p-Akt/Akt,p-mtor/mTOR protein expression levels were significantly decreased(P＜0.01).Compared with model group,the body weight and grip strength of rats with low,medium and high doses of Guipi decoction were increased(P＜0.05,P＜0.01).The protein and mRNA expression levels of IGF-1 and IGF-1R in gastrocnemius were increased(P＜0.05,P＜0.01);The expressions of Fbxo32 and Trim63 were significantly decreased(P＜0.05,P＜0.01).The ratios of P-PI3K/PI3K,p-Akt/Akt,P-mtor/mTOR protein expression levels were significantly increased(P＜0.05,P＜0.01).Conclusion Guipi Decoction has obvious improvement effect on 5-FU-induced sarcopenia model rats,which may be related to activation of IGF-1/PI3K/Akt/mTOR signaling pathway and up-regulation of IGF-1,IGF-1R,p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR protein expression.
万方数据
维普
