阿托伐他汀对EAE大鼠脊髓ICAM-1和TGF-β1表达的影响

Effect of atorvastatin on expressions of intercellular adhesion molecule-1 and transforming growth factor-β1 in the spinal cord of rats with experimental autoimmune encephalomyelitis

目的探讨阿托伐他汀对实验性自身免疫性脑脊髓炎（EAE）大鼠脊髓细胞间黏附分子-Ⅰ（ICAM-Ⅰ）和转化生长因子-β1（TGF-β1）表达的影响。方法80只清洁级健康雌性Wistar大鼠按照随机数字表法分为4组：正常对照组、EAE模型组、低剂量治疗组、高剂量治疗组．每组20只。各组再分为第14天、21天两个亚组，每个亚组10只。利用新鲜豚鼠全脊髓匀浆及完全福氏佐剂免疫Wistar大鼠建立EAE模型。低、高剂量治疗组大鼠分别给予2mg／（kg·d）、10mg／（k2·d）阿托伐他汀灌胃，正常对照组及EAE模型组应用生理盐水灌胃。观察每组大鼠发病情况并进行神经功能障碍评分，采用HE染色方法观察病理改变，免疫组化方法检测ICAM-1及TGF-β1的表达。结果与EAE模型组及低剂量治疗组比较，阿托伐他汀高剂量治疗组发病率明显减轻．炎性病灶明显减少，组织中ICAM-1表达明显减少，TGF-β1表达明显增多，差异均有统计学意义（P〈0．05）。结论阿托伐他汀可改善EAE大鼠的临床症状及病理改变，并且与剂量有关，其作用推测与减少ICAM-1表达、提高TGF-β1表达有关。

Objective To study the effect of atorvastatin on the expressions of intercellular adhesion molecule-1 （ICAM-1） and transforming growth factor-β1 （TGF-β1） in the spinal cord of rats with experimental autoimmune encephalomyelitis （EAE）. Methods Eighty healthy female Wistar rats were randomly divided into 4 groups： normal control group （n=20）, EAE model group （n=20）, low-dose treatment group （n=20） and high-dose treatment group （n=20）. Each group was equally divided into 2 sub-groups： 14-d group and 21-d group according to the day that they were sacrificed. EAE rat models were established by immunizing the rats with flesh guinea-pig spinal cord homogenate plus complete Freund＇s Adjuvat （CFA）. Rats of the treatment groups were fed with atorvastatin at dasage of 2 mg/（kg, d） and 10 mg/ （kg.d）, respectively; and rats of the normal control group and EAE model group were fed with physiological saline. The severity of EAE was scored according to the signs and symptoms, and NIHSS was performed. Pathological changes were observed with the aid of HE staining. The levels of ICAM-1 and TGF-β1 were detected by immnnohistochemistry. Results The rats in the high-dose treatment group had significantly lower incidence of disease, decreased CNS inflammation focus, lower level of ICAM-1 and higher level of TGF-β1 as compared with rats of the EAE model group and low-dose treatment group （P〈0.05）. Conclusion Atorvastatin could ameliorate EAE of rats in a dose-dependent manner, whose effect might be related to the decreased expression of ICAM-1 and increased expression of TGF-β1.