左旋咪唑对EAE大鼠中枢神经系统MCP-1、MIP-1α的影响  

Effects of Levamisole on MCP-1 and MIP-1α in the Central Nervous System of Experimental Allergic Encephalomyelitis

作　　者：卢晔芬[1] 郑荣远[1] 吴赛珍[1] 邱伟文[1] 韩钊[1] 陈国钱[1] 

机构地区：[1]温州医学院附属第一医院神经科温州医学院实验神经生物学研究所,325000

出　　处：《中国临床神经科学》2006年第6期577-583,共7页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金资助项目(编号:30470611);浙江省自然科学基金资助项目(编号:Y204133)

摘　　要：目的:了解左旋咪唑(LMS)不同阶段给药对实验性变态反应性脑脊髓炎(EAE)大鼠中枢神经系统(CNS)内MCP-1、MIP-1α表达的影响。方法:采用豚鼠脊髓匀浆免疫Wistar大鼠建立EAE模型,分别在免疫前(LMS1)、免疫同时(LMS2)、免疫后(LMS3)给予LMS10mg·kg-1,采用行为学变化观察发病情况,常规苏木精-伊红和Kluver&Barrera髓鞘染色法观察CNS病理变化,免疫组化法及原位杂交法观察MCP-1、MIP-1α的表达。结果:LMS1及LMS2组能加重行为学及病理变化(P<0.01,P<0.05),而LMS3组出现复发。免疫组化和原位杂交结果:和EAE组相比,LMS1,LMS2组MCP-1、MIP-1α的表达量明显升高(P<0.01,P<0.05)。结论:LMS能明显增加EAE大鼠CNS内MCP-1、MIP-1α的表达。提示LMS有促进EAE炎性细胞的趋化、激活作用,在免疫反应炎症细胞向CNS迁移过程中起重要的作用。Aim： To observe the effect of LMS on MCP-1 and MIP-1α in the CNS in EAE of Wistar rats. Methods： Forty-five female Wistar rats were divided into five groups： control group, EAE group, pretreatment of LMS group（LMS 1）, co-administeration of LMS group（LMS2）, administeration of LMS in recovery stage group（LMS3）. The rats were induced by guinea pig spinal cord homogenate. EAE induced rats of LMS 1, 2, 3 group received levamisole in different time. The diet, movement, body weight of the Wistar rats were daily examined, tissues were stained with hematoxylineosin and Kluver ＆ Barrera, the expression of MCP-l, MIP-1α were examined with the method of immunohistochemistry, the expression of MCP-1 mRNA was examined with the method of hybridization in situ. Results：① The change of animal behaviour： LMS1 and LMS2 increased incidence and exacerbated clinical signs. LMS3 made clinical signs relapse. ②The change of histology in CNS： EAE group showed parenchymal infiltration and perivascular cuffing with mononuclear cells and demyelination. LMS1 and LMS2 showed exacerbation of demyelinating sheaths and inflammation infiltration. LMS3 showed parenchymal infiltration and demyelination in the period of relapse.③The result of immunohistochemistry： compared with EAE group, the expression of MCP-1 and MIP-1α in LMS 1 and LMS2 increased（P 〈 0.01） during the acute phase; in the period of relapse, the number of positive cells in LMS3 increased.④ Hybridization in situ analysis： compared with EAE group, the number of cells which expressing of MCP-1 mRNA in LMS 1 and LMS2 increased（P 〈 0.01） during the acute phase; in the period of relapse, the number of positive cells in LMS3 increased. Condusion：LMS can remarkably increase the expression of MCP-1 and MIP-1α in the CNS of EAE. The results suggest that LMS could promote the chemotaxis of activated inflammatory cells which play a pathogenic role in immigration process of inflammatory cell to penetrate BBB in EAE.

关 键 词：实验性变态反应性脑脊髓炎 左旋咪唑 趋化因子 单核细胞趋化蛋白-1 巨噬细胞炎性蛋白-1Α 

分 类 号：R744.502[医药卫生—神经病学与精神病学]