阿司匹林通过抑制EphA4通路保护缺血造成的脑白质损伤  

Aspirin protects against cerebral chronic cerebral ischemia-induced white matter lesion by inhibiting EphA4 pathway

作　　者：黄冬[1] 史明[1] 陈静[1] 王静[1] 朱浩[1] 辛加仑 刘之荣[1] 

机构地区：[1]第四军医大学西京医院神经内科,西安710032

出　　处：《神经解剖学杂志》2016年第5期613-617,共5页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81471197)

摘　　要：目的:我们前期研究发现阿司匹林具有脑白质保护作用,但其机制尚不清楚。有研究报道Eph信号与白质损伤密切相关,为此本研究拟探讨大鼠脑白质损伤后阿司匹林对Eph受体表达变化的影响。方法:成年雄性SD大鼠利用双侧永久性颈总动脉结扎模型造成脑白质损伤(WML)。随机分为正常组、WML组和阿司匹林处理组(每日100 mg/kg,ip,30d),每组15只。采用Real-time PCR法检测正常组胼胝体内8种Eph受体的表达情况;免疫荧光染色检测Eph受体是否表达在少突胶质细胞中;Western Blot检测各组Eph受体和髓鞘碱性蛋白(myelin basic protein,MBP)的表达变化及相互关系。结果:Real-time PCR结果:8种Eph受体中,EphA4的mRNA表达水平最高。EphA4与CNPase的免疫荧光染色示:EphA4表达于胼胝体内的少突胶质细胞。与正常组相比,WML组中EphA4^+细胞数量增多(P<0.05),阿司匹林处理后EphA4^+细胞数量减少(P<0.05)。Western Blot结果显示:与正常组比较,WML组胼胝体部EphA4表达升高(P<0.05),但MBP蛋白表达下降(P<0.05);阿司匹林处理后,可下调EphA4(P<0.05)、上调MBP的表达水平(P<0.05),二者呈显著负相关。结论:阿司匹林可能通过抑制EphA4通路保护缺血造成的脑白质损伤。Objective： Our previous study has showed that aspirin protects against the white matter lesion（ WML） but its mechanism is still unclear. Studies have reported that Eph signal is closely related to the WML. Thus,this study aims to examine the changes of Eph receptor expression after administration of aspirin in the WML models. Methods： Adult male SD rats were subjected to permanent and bilateral common carotid artery occlusion to cause cerebral white matter lesions. All rats were randomly divided into normal group,the WML group,and the WML group treated with aspirin（ 100 mg / kg / d,ip,30 d）,（ n = 15） for each group. Real-time PCR was used to examine eight subunits of Eph receptors expression in the corpus callosum of the normal rats. The expression of Eph receptors in the oligodendrocytes were detected by using double immunofluorescent staining. Western Blot was used to examine the expression of protein and the relationship of the Eph receptors and myelin basic protein（ MBP）. Results： Real-time PCR results showed that EphA4 mRNA expression was at the highest level among eight subunits of Eph receptors in the rat corpus callosum. Double immunofluorescent staining of EphA4 receptors and CNPase（ specific markers of oligodendrocytes） showed that the oligodendrocytes in the corpus callosum expressed EphA4 receptors. Compared with the normal group,the number of EphA4~＋cells was significantly increased in the WML group（ P〈0. 05）. The number of EphA4~＋cells was significantly decreased after aspi-rin treatment（ P〈0. 05）. Western Blot showed that EphA4 receptors expression were significantly increased in the WML group compared with the normal group（ P〈0. 05）,but the MBP protein expression was significantly decreased（ P〈0. 05）. EphA4 receptor expression was downregulated after aspirin treatment（ P〈0. 05）,but the MBP protein expression was upregulated（ P〈0. 05）. The expression of EphA4 and MBP have significant negative correlation. Conclusion： Aspirin may pr

关 键 词：阿司匹林 脑白质损伤 胼胝体 EphA4 脑缺血 大鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]