Abstract

Objective To investigate the therapeutic effects of simvastatin on experimental autoimmune encephalomyelitis(EAE)and explore its mechanisms. Methods Fifty-five Wistar rats were randomly divided into EAE group (n=15),.STATINS group(n=15),triptolide(TP)group(n=15)and normal control group(n=10).In STATINS group,the rats were given simvastatin and the changes in the expressions of P53,interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and transforming growth factor-β(TGF-β)were observed,with triptofide as the positive control.Results Compared to the EAE group,the rats in STATINS group had significantly lowered incidence of EAE,mild symptoms,reduced body weight loss and lesion foci number,and prolonged latency of EAE onset(P<0.05).The rats in the TP group also exhibited significantly milder symptoms and fewer lesion foci than the EAE group(P<0.05),but the body weight changes.,latency or incidence of EAE had no significant difference between the two groups(P>0.05).Simvastatin significantly suppressed the expression of IL-6 and TNF-α and increased the expressions of P53 and TGF-β in rats with EAE,whereas TP only resulted in significant suppression of TNF-αexpression(P<0.05).The expressions of P53 and TGF-β were significantly higher in STATINS group than in TP group(P<0.05),but the expressions of TNF-α and IL-6 were comparable between the two groups(P>0.05). Conclusions Simvastatin Can suppress EAE more effectively than TP by suppressing the expressions of the inflammatory factors such as IL-6 and TNF-α and promoting the expressions of P53 and TGF-β. Key words: Multiple sclerosis; Experimental autoimmune encephalomyelitis; P53; Cytokines; Simvastatin

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