自身免疫性脑脊髓炎小鼠脑内LINGO-1的表达  

LINGO-1 Expression of brain tissue in Experimental Autoimmune Encephalomyelitis Mouse

作　　者：汪春娟[1] 郭守刚[2] 屈传强[2] 张杰 付佩彩[1] 唐荣华[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030 [2]山东大学附属省立医院神经内科 [3]山东省邹平市人民医院神经内科

出　　处：《中华医学杂志》2014年第15期1184-1188,共5页National Medical Journal of China

基　　金：国家自然科学基金（81171171,30970991）;山东省自然科学基金（ZR2009CQ028,Y2007C043）

摘　　要：目的观察自身免疫性脑脊髓炎（EAE）小鼠发病后不同时间大脑组织中LINGO-1表达水平的变化。方法将C57／BL6小鼠完全随机化分为EAE模型组（15只）、佐剂组（15只）和对照组（15只），在发病第1、7、14、21、30天取大脑半球组织进行实时定量RT—PCR和Western印迹检测，观察LINGO-1的表达差异。同时应用Western印迹检测不同时间点RhoA、RhoA磷酸化形式（P—RhoA）的变化。结果EAE模型组小鼠发病后第1、7、14天LINGO-1mRNA表达水平是对照组的（4．63±0．25）、（2．72±0．12）和（1．98±0．16）倍（P〈0．01，P〈0．01，P〈0．05），至第30天时接近于对照组（P〉0．05）；模型组LINGO—1蛋白表达在发病后第1、7、14、21、30天分别为对照组的（2.11±0．15）、（3．15±0．09）、（2．45±0．12）、（1．89±0．17）和（1．21±0．05）倍（P〈0．05，P〈0．01，P〈0．05，P〈0．05，P〈0．05，P〈0．05）；模型组小鼠p-RhoA蛋白表达也呈上调趋势，在造模成功1、7d上调最明显（P〈0．01）。而RhoA蛋白的表达无明显变化。结论LINGO-1在EAE小鼠脑组织中表达上调并呈-定规律性改变，可能通过RhoA激活抑制髓鞘修复。临床上针对多发性硬化的LINGO-1阻断治疗应在发病后尽早进行。Objective To observe the changes of LINGO-1 expression with time after onset in EAE mouse. Methods C57/BL6 mice were completely randomly divided into EAE model group （n = 15 ）, adjuvant group（ n = 15） and control group（ n = 15）. LINGO-1 expression of brain tissue was detected on day 1,7,14,21 and 30 after onset by RT-PCR and Western blot. RhoA and p-RhoA expression of brain tissue was analysed by Western blot. Results The LINGO-lmRNA levels in EAE model group were markedly higher than control group on day 1,7and 14 after onset （4. 63 ±0.25,2.72 ±0. 12,1.98 ±0. 16, P 〈0. 01, P 〈 0. 01, P 〈 0. 05 ）. On day 30, Lingo-1 mRNA was close to control group. Expression levels of Lingo-1 protein on day 1,7,14,21,30 were higher than control group （2. 11 ＋ 0. 15,3.15 ± 0. 09,2. 45 ± 0. 12,1.89 ± 0. 17,1.21 ± 0. 05,P 〈 0. 05, P 〈 0. 01, P 〈 0.05, P 〈 0. 05,P 〈 0. 05. The levels of p-RhoA protein increased in EAE and the peak appeared on day 1 and day 7 （P 〈 0. 01 ）. And there was no difference on RhoA expression among different groups. Conclusions LINGO-1 expression of brain tissue of EAE mouse upregulates and changes with time after onset, which may inhibit myelination by RhoA activation. In clinic, the antagonist of LINGO-1 for MS should be applied as soon as possible.

关 键 词：脑脊髓炎 自身免疫性 实验性 多发性硬化 LINGO-1蛋白 

分 类 号：R744[医药卫生—神经病学与精神病学]