口服盐酸法舒地尔治疗小鼠EAE有效性初探

发布时间：2018-09-01 15:43

【摘要】：目的:探讨盐酸法舒地尔口服对实验性自身免疫性脊髓炎(EAE)的治疗效果及机制。方法:采用髓鞘少突胶质细胞糖蛋白33-35肽(MOG35-55)免疫雌性C57BL/6小鼠建立慢性EAE模型,随机分为EAE模型组和法舒地尔治疗组。免疫后第3天,对照组予以灌胃生理盐水,治疗组予以法舒地尔,每天1次至免疫后第27天。比较2组小鼠体重变化和临床评分。第28天处死动物,脊髓冰冻切片进行髓鞘染色和HE染色,流式细胞术检测脾细胞M1型和M2型巨噬细胞的表型,ELISA法检测脾细胞培养上清液白细胞介素10(IL-10)、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的释放。结果:法舒地尔口服推迟EAE发病时间,减缓EAE症状,减少体重下降,减少EAE髓鞘脱失和中枢神经系统炎症浸润,抑制M1型巨噬细胞CD16/32表达,增加M2型巨噬细胞CD206和IL-10表达,同时抑制炎症细胞因子IL-1β和TNF-α的释放。结论:法舒地尔口服具有良好的治疗效果,可明显减轻中枢神经系统的髓鞘脱失和炎症病灶。其作用机制可能使M1型巨噬细胞向M2型转化,从而抑制炎症细胞因子释放。
[Abstract]:Aim: to investigate the therapeutic effect and mechanism of famdil hydrochloride orally on experimental autoimmune myelitis (EAE). Methods: female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein 33-35 peptide (MOG35-55) to establish chronic EAE model and were randomly divided into EAE model group and fasudil treatment group. On the 3rd day after immunization, the control group was given normal saline by stomach, and the treatment group was given fasudil once a day until the 27th day after immunization. The changes of body weight and clinical score were compared between the two groups. On the 28th day, the animals were killed. The spinal cord was stained by myelin sheath and HE staining. The expression of interleukin-10 (IL-10), interleukin-1 尾 (IL-1 尾) and tumor necrosis factor 伪 (TNF- 伪) in the supernatant of splenocyte culture were detected by flow cytometry. Results: fasudil orally delayed the onset of EAE, alleviated the symptoms of EAE, reduced weight loss, reduced EAE demyelination and inflammatory infiltration of the central nervous system, inhibited the expression of CD16/32 in M1 macrophages, and increased the expression of CD206 and IL-10 in M 2 macrophages. The release of inflammatory cytokines IL-1 尾 and TNF- 伪 was inhibited at the same time. Conclusion: the oral administration of fasudil has a good therapeutic effect and can significantly reduce demyelination and inflammation in the central nervous system. The mechanism may inhibit the release of inflammatory cytokines by transforming M 1 macrophages into M 2 type macrophages.
【作者单位】：山西医科大学第一临床医学院神经内科;山西大同大学脑科学研究所;大同市第五人民医院神经科;山西中医学院第三中医院脑病科卫生部国家临床重点专科;复旦大学华山医院神经病学研究所;
【基金】：国家自然科学基金资助项目(No.81070957;No.81272163) 山西中医学院“2011计划”培育计划资助项目(No.2011PY-1) 2013年度国家国际科技合作专项项目(No.2013DFA30700) 山西省青年自然科学基金资助项目(No.2012021034-2) 山西大同大学青年科学研究项目(No.2010Q6)
【分类号】：R-332

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