摘要
目的探讨辛伐他汀(STATINS)对实验性自身免疫性脑脊髓炎(EAE)的作用及机理。方法Wistar大鼠55只采用随机数字表法分为EAE组(15只)、STATINS组(15只)、雷公藤(TP)组(15只)、正常对照组(10只)。使用STATINS干预EAE大鼠,以TP为阳性对照,观察大鼠P53蛋白、IL-6、TNF-α、TGF-β的表达变化。结果与EAE组相比,STATINS组发病率降低、临床症状减轻、体质量下降减少、病灶数减少、潜伏期延长,而TP组临床症状减轻、病灶数减少,差异均有统计学意义(P〈0.05),TP组体质量变化、潜伏期、发病率无明显变化,差异无统计学意义(P〉0.05);STATINS组IL-6和TNF-α的表达降低,P53蛋白和TGF-β的表达增高;TP组仅TNF-α的表达降低,差异均有统计学意义(P〈0.05)。与TP组相比较,STATINS组P53蛋白与TGF-β的表达增加,差异有统计学意义(P〈0.05),而TNF-α及IL-6的表达差异无统计学意义(P〉0.05)。结论STATINS可以有效抑制EAE,其可能的机制是抑制IL-6和TNF-α等促炎症因子的表达,促进P53蛋白与TGF-β的表达,效果可能优于TP。
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 triptolide 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 loci 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-α expression (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.
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2009年第4期367-371,共5页
Chinese Journal of Neuromedicine
基金
山西省2003年度回国留学人员科研基金(2003-69)
国家人口和计划生育委员会科研项目(C1-42)