黄连素对EAE大鼠小胶质细胞及细胞因子的影响

Effects of Berberine on Microglia and Cytokines in Rats with Experimental Autoimmune Encephalomyelitis

目的探讨黄连素(berberine,Ber)对实验性自身免疫性脑脊髓炎(encephalomyelitis,EAE)大鼠脊髓中小胶质细胞及IFN-γ、TNF-α和IL-10水平的影响。方法 Lewis大鼠24只随机分为3组:对照组、模型组和Ber组。采用免疫组化法检测腰髓中小胶质细胞的变化;采用ELISA法检测大鼠外周血和颈髓中促炎因子IFN-γ、TNF-α和抑炎因子IL-10的变化。结果模型组8只大鼠全部出现典型的EAE行为学改变,Ber组有3只大鼠出现EAE行为学改变。与模型组相比,Ber组大鼠外周血中IFN-γ和TNF-α表达降低(P<0.05),而IL-10的表达无明显变化;脊髓中活化的小胶质细胞数量减少,IFN-γ和TNF-α表达降低(P<0.05),IL-10表达增加(P<0.05)。结论 Ber能抑制大鼠EAE的病情,其机制可能与抑制小胶质细胞的活化,下调IFN-γ、TNF-α的表达,并且上调IL-10的表达有关。

OBJECTIVE To explore the effects of berberine（Ber） on experimental autoimmune encephalomyelitis（EAE） and the changes of the levels of microglia, IFN-γ, TNF-α and IL-10 in spinal cord. METHODS Twenty four Lewis rats were randomly divided into three groups： control group, model group and Ber group. The change of activated microglia which expressing ibal in lumbar cords was counted by immunohistochemistry. Expression levels of IFN-γ, TNF-α and IL-10 in serum and cervical cord were quantified by ELISA. RESULTS Eight rats in model group completely showed neurological signs of typical EAE. However, only three rats in Ber group demonstrated neurological signs of typical EAE. ELISA analysis showed that the expression of IFN-γ and TNF-α decreased significantly in the serum in Ber group compared with model group（P〈0.05）, IL-10 expression was not changed significantly. Immunohistochemical results showed that the active number of microglia was significantly inhibited in Ber group compared with the model group（P〈0.05）. Tissue ELISA analysis showed that the expression of IFN-γ and TNF-α decreased significantly（P〈0.05）, and the expression of IL-10 increased in the spinal cord in Bet group compared with model group（P〈0.05）. CONCLUSION Ber has an effect on prevention on occurence of EAE in Lewis rats, may be related to inhibition of microglia activation and dowuregulation of IFN-γ TNF-α expression and upregulation of IL-10.