雌激素受体α对实验性自身免疫性脑脊髓炎小鼠TIMP-1及TIMP-2表达的影响  

Eestrogen receptor α affected expression of TIMP-1 and TIMP-2 in experimental autoimmune encephalomyelitis mice

作　　者：朱加应[1] 王建怡[2] 李玫[1] 瞿浩[1] 胡晓[1] 

机构地区：[1]贵州省人民医院神经内科,贵州贵阳550002 [2]贵州省人民医院小儿内科,贵州贵阳550002

出　　处：《中风与神经疾病杂志》2013年第6期508-512,共5页Journal of Apoplexy and Nervous Diseases

基　　金：贵州省科技厅攻关项目[黔科合sy(2009)3054];贵州省优秀科技教育人才省长专项资金[黔省专合字(2010)86号];贵州省科技厅攻关项目[黔科合SY字(2012)3143号];贵州省科学技术基金项目[黔科合J字(2011)2281号]

摘　　要：目的以实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)作为多发性硬化(multiple sclerosis,MS)的动物模型,初步探讨雌激素和雌激素受体α(estrogen receptorα,Erα)在EAE中的抗炎作用及其作用机制。方法在小鼠侧脑室立体定位注射Erα重组慢病毒,鉴定Erα重组慢病毒在体感染中枢神经系统(central nervous system,CNS)的最佳剂量。将雌二醇及Erα重组慢病毒干预EAE小鼠与对照组比较,观察各组小鼠的临床症状及体重的变化,通过H&E染色及Luxol fast blue-H&E染色对比各组炎症反应及脱髓鞘情况,以实时荧光定量PCR及Western blot方法检测金属蛋白酶组织抑制因子-1(tissue-inhibitors of matrix metalloprotein-ase-1,TIMP-1)及TIMP-2。结果 15μl Erα重组慢病毒能感染小鼠CNS。与对照组相比,雌二醇及过表达Erα可以降低EAE小鼠的发病率、体重丢失及临床症状,减轻脑和脊髓中炎性细胞浸润和神经纤维的髓鞘脱失,在发病急性期增加TIMP-1及TIMP-2,减轻在缓解期TIMP-1、TIMP-2的病理性表达增高。结论雌激素及Erα可以抑制EAE的炎症反应,该作用机制可能是通过增加EAE小鼠急性发病期脑组织中TIMP-1及TIMP-2实现的。Objective To investigate the anti-inflammatory effects/mechanism（s） of estrogen and estrogen receptor α（Erα） in an experimental autoimmune encephalomyelitis（EAE） mouse model of multiple sclerosis（MS）.Methods We sterotaxically injected Erα recombinant lentivirus into the lateral ventricle of mice brain,and then identified to obtain the optimal dose in central nervous system（CNS）.EAE mice treated with estradiol or Erα was overexpressed,and the clinical symptoms and body weight of the experimental mice were compared with control group.The inflammatory response of EAE mice was studied by HE staining and luxol fast blue-HE staining was used to analyze demyelination,and tissue inhibitors of matrix metalloproteinase-l（TIMP-1） and TIMP-2 were measured by real-time quantitative PCR and western blot.Results 15 μl Erα recombinant lentivirus infected the CNS of C57BL/6 mice successfully.Comparison with control group,treatment of estradiol,Erα recombinant lentivirus could reduce the incidence,clinical symptoms and body weight loss of EAE mice,inhibit infiltration of brain and spinal cord by inflammatory cells and demyelination of nerve fibers.At the same time in incidence of acute phase,estradiol and Erα recombinant lentivirus could increase the expressions of TIMP-1,TIMP-2.And in remission phase,the pathological addition of TIMP-1,TIMP-2 were reduced.Conclusion Estrogen and Erα inhibit inflammatory response in the EAE mouse model.The mechanism might be that there were increased TIMP1 and TIMP2 in brain tissue in acute onset of EAE mouse.

关 键 词：多发性硬化 实验性自身免疫性脑脊髓炎 雌激素 雌激素受体Α 金属蛋白酶组织抑制因子 

分 类 号：R744.53[医药卫生—神经病学与精神病学]