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目的探讨17β-雌二醇对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)大鼠中枢神经系统Rho激酶表达的影响及相关机制。方法 75只雌性Wistar大鼠分为正常组、模型组、雌激素组、DMSO对照组和雌激素+雌激素核受体抑制剂ICI组。雌激素组每日皮下注射17β-雌二醇20μg/(kg.d),连续10 d。雌激素+ICI组于17β-雌二醇注射前先给予雌激素核受体抑制剂ICI 182780 5 mg/(kg.d),比较各组大鼠神经功能评分;HE染色观察病理学改变;免疫组织化学和Western blot观察Rho激酶表达的变化。结果与对照组和模型组分别比较,雌激素组发病潜伏期延长,神经功能评分降低;HE染色示雌激素组炎性细胞浸润减少;免疫组化检测结果显示,雌激素组Rho激酶阳性细胞数(8.36±1.57)明显低于模型组[(17.55±1.70),P<0.01];Western blot检测结果显示,雌激素组蛋白表达相对值(0.833±0.022)显著低于模型组[(1.013±0.060),P<0.05];雌激素+ICI组Rho激酶阳性细胞数(18.90±2.39)和蛋白表达(1.141±0.046)显著高于雌激素组(P<0.05)。结论 17β-雌二醇能抑制EAE大鼠Rho激酶的表达,这种抑制作用是通过经典的雌激素核受体通路实现的。
Objective To investigate the effect of 17β-estradiol on Rho-kinase expression in central nervous system of experimental autoimmune encephalomyelitis (EAE) rats and its related mechanism. Methods 75 female Wistar rats were divided into normal group, model group, estrogen group, DMSO control group and estrogen + estrogen nuclear receptor inhibitor ICI group. The estrogen group was injected subcutaneously with 17β-estradiol 20μg / (kg.d) for 10 days. The estrogen + ICI group was given ICI 182780 5 mg / (kg · d) before 17β-estradiol injection, and the neurological function scores of the rats in each group were compared. The pathological changes were observed by HE staining. Histochemistry and Western blot were used to observe the changes of Rho kinase expression. Results Compared with the control group and the model group, the latent period of onset in estrogen group was longer and the score of neurological function was decreased. The inflammatory cell infiltration in estrogen group was reduced by HE staining. The results of immunohistochemistry showed that the number of Rho kinase positive cells in estrogen group 8.36 ± 1.57) was significantly lower than that of the model group [(17.55 ± 1.70), P <0.01]. Western blot showed that the relative value of the expression of estrogen histone (0.833 ± 0.022) was significantly lower than that of the model group [(1.013 ± 0.060) , P <0.05]. The number of Rho-kinase positive cells (18.90 ± 2.39) and protein expression (1.141 ± 0.046) in estrogen + ICI group were significantly higher than those in estrogen group (P <0.05). Conclusion 17β-estradiol can inhibit the Rho kinase expression in EAE rats through the classical estrogen receptor pathway.