雌激素对实验性自身免疫性脑脊髓炎小鼠的治疗作用及对基质金属蛋白酶-9表达的影响  

Estrogen decreasing matrix metalloproteinase-9 gene expression in mice with experimental autoimmune encephalomyelitis

作　　者：胡晓[1] 朱加应[2] 黄伟琨[3] 万兴[4] 王建怡[5] 

机构地区：[1]贵州省人民医院神经内科,贵阳550002 [2]贵州省人民医院急诊科,贵阳550002 [3]贵州省人民医院口腔科,贵阳550002 [4]贵州省人民医院肿瘤科,贵阳550002 [5]贵州省人民医院小儿内科,贵阳550002

出　　处：《中华神经科杂志》2011年第7期468-472,共5页Chinese Journal of Neurology

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项目[黔省专合字（2010）86号]

摘　　要：目的探讨雌激素对实验性自身免疫性脑脊髓炎（EAE）小鼠中枢神经系统（CNS）中基质金属蛋白酶-9（MMP-9）表达的影响。方法用MOG35-55多肽诱发60只EAE小鼠模型，做去卵巢术。分为治疗组和对照组，治疗组予雌激素治疗。比较2组EAE小鼠的临床症状评分。取脑和脊髓，行HE染色观察各组EAE小鼠炎症反应；实时荧光定量PCR及免疫荧光染色法检测各组EAE小鼠CNS中MMP-9的表达。结果治疗组EAE小鼠与对照组相比临床症状减轻（治疗组3．23±0．83，对照组1．62±1．00，t=3．811，P〈0．05）、发病率降低（治疗组8／30，对照组28／30）；HE染色显示治疗组炎症细胞浸润（急性期0．895±0．206，缓解期0．752±0．302，慢性期0．732±0．183）较对照组（急性期3．472±0．635，缓解期2．881±0．662，慢性期1．891±0．482）减少（t=8．622、6．543、5．027，均P〈0．01），实时荧光定量PCR及免疫荧光染色结果示治疗组EAE小鼠CNS中MMP-9表达降低。结论雌激素能抑制EAE小鼠CNS中MMP-9的表达，减轻EAE小鼠临床症状及炎症反应。Objective To study the regulation effect of estrogen in expression of matrix metalloproteinase-9 （MMP-9） in the central nervous system （CNS） in mice with experimental autoimmune encephalomyelitis （EAE）. Methods The 60 mice were overiectomized and 2 weeks later EAE was induced with MOG35-55 peptide in these mice. They were divided into a treatment group and a control group. The treatment group was treated with estrogen and the control group was given PBS. Clinical symptoms in these two groups were scored and compared. HE staining was used to observe inflammation in the brain and spinal cord. The MMP-9 expression in the CNS was examined by quantitative real-time PCR and immunofluorescence staining. Results The incidence of disease was lower （treatment and control group were 8/30 and 28/30 respectively） and clinical symptoms were milder （treatment and control group were 3.23±0. 83 and 1.62±1. 00 respectively, t =3. 811 and P 〈0. 05） in the treatment group than those in the control group. HE staining showed the decreased infiltration of inflammatory cell in the treatment group （Treatment group： inflammatory score were 0. 895±0. 206, 0. 752±0. 302, 0. 732±0. 183 in acute, relief and chronic phase respectively; Control group： inflammatory score were 3. 472±0. 635, 2. 881±0. 662, 1. 891±0. 482 in acute, relief and chronic phase respectively, t = 8. 622, 6. 543 and 5. 027, all P 〈 0. 05）. The quantitative real-time PCR and immunofiuorescence staining showed that the expression of MMP- 9 in the CNS was decreased in the treatment group. Conclusion Estrogen may decrease MMP-9 expression in the CNS, reduce inflammation and clinical symptoms in mice with EAE.

关 键 词：脑脊髓炎 自身免疫性 实验性 雌激素类 基质金属蛋白酶9 小鼠 

分 类 号：R965[医药卫生—药理学]