【作者】 周建波；

【导师】 曾丽；

【作者基本信息】 广西医科大学 ， 神经病学， 2011， 硕士

【摘要】 目的探讨米诺环素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(Central nervous system, CNS)凋亡相关蛋白Fas和Bcl-2表达的影响,以及对CNS内组织损伤的作用。方法将50只雌性Wistar大鼠随机分为正常对照组10只,EAE模型组20只,米诺环素治疗组20只；以豚鼠全脊髓匀浆(Guinea pig spinal cord homogenate, GPSCH)为抗原免疫大鼠建立EAE模型。然后治疗组给予米诺环素灌胃,而对照组和模型组则给予相同剂量的生理盐水灌胃。观察各组大鼠发病情况,采取HE染色及髓鞘染色观察组织病理学变化,以免疫组化检测各组大鼠CNS内Fas和Bcl-2蛋白的表达。结果EAE模型组的行为学评分高于米诺环素治疗组(P=0.018)。HE染色可见治疗组CNS内炎性细胞浸润较模型组减少；髓鞘染色则见各发病大鼠CNS组织结构疏松,出现弥漫性脱髓鞘改变,其中评分较高的大鼠病变相对严重,且米诺环素治疗组较EAE模型组稍轻。Fas的表达各组平均光密度和阳性细胞数模型组均高于治疗组(P<0.05),脑干和脊髓的平均光密度在治疗组和对照组之间没有明显差异(P>0.05)。Bcl-2的表达除脑干阳性细胞数外各部位平均光密度和细胞数治疗组均高于模型组,而对照组低于模型组(P<0.05),模型组和治疗组脑干的阳性细胞数高于对照组(P<0.05)。结论米诺环素可以使EAE大鼠CNS内Fas蛋白的表达下调、Bcl-2蛋白的表达上调；并可能通过介导Fas和Bcl-2的表达干预凋亡调节免疫反应,减轻CNS组织损伤而对EAE起到一定的治疗作用。更多还原

【Abstract】 ObjectiveTo investigate the effect of minocycline on expression of Fas and Bcl-2 in CNS of rats with experimental autoimmune encephalomyelitis(EAE), and the effect to damage in CNS of EAE.MethodsFifty female Wistar rats were divided into three groups randomly, normal control group(10), EAE model group(20) and minocycline-treatment group(20). EAE was induced in rats by immunization with guinea pig spinal cord homogenate (GPSCH). The rats in the treatment group were given minocycline (90mg/kg, the first day; 45mg/kg, the following days) by gavage, and the rats in the control and model groups were given normal saline by gavage. The symptom of rats in three groups was observed and the pathological changes were determined by HE staining and myelin staining, and the expression of Fas and Bcl-2 in the CNS were estimated by immunohistochemical method.ResultsThe behavioral scores of model group were higher than treatment group (P=0.018). In the treatment group inflammation cells were less than model group around the vessels observed by HE staining; the structure of tissue in the CNS of rats with high scores becomes soft and diffuse demyelination, and the treatment group in which was litter damage than model group observed by myelin staining. The expression of Fas:compared with treatment group, the average density and positive cells were higher in every part of model group (P<0.05); There was no significant difference in the average density of brain stem and spinal cord between treatment and control group (P>0.05). The expression of Bcl-2:the average density and positive cells of treatment group were more than model group in every part except brain stem, and the control group was lower than model group (P<0.05); the positive cells in brain stem of model and treatment group were more than normal control group (P<0.05)ConclusionsMinocycline can regulate the expression of Fas and Bcl-2 proteins in EAE; it may have influence on apoptosis in EAE and then exert immunoregulatory actions on it. Minocycline can reduce the damage in CNS of EAE and may have therapeutic effects on EAE.更多还原