他克莫司对大鼠实验性变态反应性脑脊髓炎的实验性治疗  

Experimental study of tacrolimus for experimental autoimmune encephalomyelitis in rats

作　　者：石海波[1] 王顺和[1] 郑娟[1] 李晗宇[1] 姜蓉[2] 唐艳 陈舜琦 张凌 

机构地区：[1]重庆医科大学基础医学院病理学教研室,重庆400016 [2]重庆医科大学干细胞与组织工程实验室,重庆400016 [3]重庆酉阳县人民医院妇产科,重庆409800 [4]重庆开县人民医院泌尿科,重庆405427 [5]重庆秀山县人民医院病理科,重庆409900

出　　处：《重庆医科大学学报》2010年第3期367-371,共5页Journal of Chongqing Medical University

摘　　要：目的:研究新型免疫抑制剂他克莫司(Tacrolimus,FK506)对大鼠实验性变态反应性脑脊髓炎(Experimental autoimmune encephalomyelitis,EAE)的治疗作用和作用机制,并与已论证的传统治疗方法甲基泼尼松龙对EAE实验治疗做临床对比其疗效。方法:豚鼠脊髓匀浆和完全福氏佐剂制成的混合液诱导SD大鼠建立EAE模型,免疫10d后将FK506分别以1mg/kg,0.5mg/kg剂量给予每日腹腔注射EAE大鼠,连续给药10d,观察其发病情况,外周血T淋巴细胞CD3、CD4、CD8、NK细胞比率,免疫后30d,观察脑、脊髓组织病理变化,免疫组织化学生长相关蛋白43(Growth associated protein43,Gap-43)显示神经再生的形态学证据。结果:FK506能减轻EAE的临床症状,促进EAE的临床缓解和恢复;减轻中枢神经系统的炎症浸润;减轻髓鞘和轴突损伤,促进轴突再生作用,且停药后未见动物复发。结论:FK506对实验性变态反应性脑脊髓炎有一定的实验性治疗作用。Objective：To explore the efficacy and therapeutic mechanism of immune inhibitor tacrolimus（FK506） for experimental autoimmune encephalomyelitis rats and compare the efficacy of FK506 and confirmed traditional methyllprednisolone.Methods：the guinea pig spinal cord homogenate in complete freund＇s adjuvant was used to induce the acute EAE in SD rats FK506 at the dosage of 1 mg/kg and 0.5 mg/kg were intraperitoneally injected to EAE rats respetively for daily for ten days.Clinical features were observed,their peripheral blood lymphocytes CD3,CD4,CD8 and NK subsets were counted,pathology changes of brain and spinal cord were observed,and the evidence of nerve regeneration was shown by immunohistochemistry stain.Result：FK506 could relieve remits the clinical phenonoue of EAE promote the climical and release and recoveny of EAE,decrease the inflammatory infiltration in the CNS,decrease demyelination and axonal damage in CNS,promote for axons regeneration.Furthermore,no replase after stopping drug was observed.Conclusion：FK506 as a immune inhibitor can be used the Autoimmune disease,such as EAE.

关 键 词：多发性硬化 实验性变态反应性脑脊髓炎 大鼠 他克莫司 

分 类 号：R453.9[医药卫生—治疗学]