Effects of p-coumaric acid on immune balance and skeletal muscle mitochondrial biogenesis in rats with myasthenia gravis
Objective To explore the therapeutic effect of p-coumaric acid(p-CA)on myasthenia gravis(MG)rats and its possible mechanism.Methods The female Lewis rats were randomly divided into 5 groups:control group,model group,low dose p-coumaric acid group(L-p-CA),medium dose p-coumaric acid group(M-p-CA)and high dose p-coumaric acid group(H-p-CA),with 12 rats in each group.The rats in control group were unmodeled,and the rats in the other groups were subcutaneously injected with acetylcholine receptor(AChR)alpha subunit 97-116 peptide sequence(Rα97-116)to induce MG models.After modeling,the rats in L-p-CA group,M-p-CA group and H-p-CA group were intragastrically fed with 1 mL of 50,100,200 mg/kg p-coumaric acid solution respectively,while the rats in control group and MG group were intragastrically fed with 1 mL corn oil.The rats in each group were treated for 4 weeks.The clinical symptoms of rats were scored by Lennon grading method,and the attenuation rate of low frequency repetitive nerve stimulation(RNS)was measured.The morphology of gastrocnemius muscle was observed by HE staining.The serum levels of AChR antibody(AChR-Ab),interferon gamma(IFN-γ)and interleukin-4(IL-4)were detected by ELISA method.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in gastrocnemius muscle were detected by different kits.The protein expressions of peroxisome proliferator activated receptor γ coactivator-1α(PGC-1α),phosphorylated AMP dependent protein kinase α(p-AMPKα),AMPKα,nuclear respiratory factor 1(NRF1)and mitochondrial transcription factor A(TFAM)in gas-trocnemius muscle were detected by Western blot.The expression of TFAM in gastrocnemius muscle was observed by immunofluores-cence staining.Results Compared with control group,Lennon score and RNS attenuation rate were significantly increased in MG group(P<0.05),serum AChR-Ab and IFN-γ levels were significantly increased(P<0.05),the injury of gastrocnemius muscle was found,SOD and GSH-Px levels,PGC-1α,p-AMPKα,NRF1 and TFAM protein expressions in gastrocnemius muscle were significantly decreased(P<0.05),TFAM relative fluorescence intensity was significantly decreased(P<0.05),and MDA level was significantly increased(P<0.05).Compared with MG group,Lennon score and RNS attenuation rate were significantly decreased in L-p-CA group,M-p-CA group and H-p-CA group(P<0.05),serum AChR-Ab and IFN-γ levels were significantly decreased(P<0.05),the gastrocne-mius muscle injury was significantly improved,SOD and GSH-Px levels,PGC-1α,p-AMPKα,NRF1 and TFAM protein expressions in gastrocnemius muscle were significantly increased(P<0.05),TFAM relative fluorescence intensity was significantly increased(P<0.05),and MDA level was decreased(P<0.05).Compared with L-p-CA group and M-p-CA group,Lennon score and RNS attenuation rate were significantly decreased in H-p-CA group(P<0.05),serum AChR-Ab and IFN-γ levels were significantly decreased(P<0.05),the gastrocnemius muscle injury was significantly improved,SOD and GSH-Px levels,PGC-1α,p-AMPKα,NRF1 and TFAM protein expressions in gastrocnemius muscle were significantly increased(P<0.05),TFAM relative fluorescence intensity was significantly increased(P<0.05),and MDA level was decreased(P<0.05).Conclusion The p-coumaric acid plays a good therapeutic effect on MG rats by improving the immune balance and activating the mitochondrial biogenesis mediated by AMPK/PGC-1α signal pathway.
myasthenia gravisp-coumaric acidinterferon gammaoxidative stressmitochondrial biogenesisimmune balancehelper T cells
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