NMDA受体亚单位NR2A在凝血酶诱导的脑出血后脑损伤中的研究  

Mechanism of NMDA Receptor Subunit NR2A in Thrombin-induced Brain Injury after Experimental Intracerebral Hemorrhage in Rats Brain

作　　者：吴保鑫 侯玉超[1] 沈霞[2] 花放[2] 张丽[3] 崔桂云[2] 

机构地区：[1]江苏省徐州市沛县人民医院神经内科,221600 [2]徐州医学院附属医院神经内科,221002 [3]南京医科大学附属脑科医院老年神经科,210029

出　　处：《中国临床神经科学》2013年第5期491-497,共7页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金课题(编号:81271344)

摘　　要：目的探讨NMDA受体亚单位NR2A在脑出血后脑损伤中的作用机制。方法成年雄性SD大鼠随机分为生理盐水组,脑出血组,凝血酶组,凝血酶+阿加曲班组。各组在手术后48 h采用不同方法观察其分布及动态变化规律。结果NMDA受体亚单位NR2A在72 h达高峰,阿加曲班可以减少其在72 h时的表达。阿加曲班可以改善血脑屏障的通透性、减轻脑水肿。结论 NMDA受体亚单位NR2A参与了脑出血后脑损伤的病理生理过程;阿加曲班通过抑制NMDA受体亚单位NR2A的激活而发挥神经保护作用。Aim To investigate the mechanisms underlying the role of NMDA receptor subunit NR2A in the thrombin-induced brain injury. Methods Adult male Sprague-Dawley rats(250-300 g) were randomly divided into 4 groups to establish the rats model: Normal saline(NS) group, intracerebral hemorrhage(ICH) group, thrombin(TM) group and thrombin(TM)+argatroban(Arg) group. The rats of each group were killed 48 hours after operation. The water content of brain was measured by comparing wet and dry weight of brain collected from perihematoma, and the permeability of blood brain barrier(BBB) was evaluated by Evans blue(EB) contents. The expression and distribution of f NMDA receptor subunit NR2A were measured by immunohistochemistry and Western-bolt at different time points(0 h, 0.5 h, 6 h, 24 h, 72 h, 120 h) in ICH group and TM group. Results The results from immunohistochemistry and Western-bolt analysis showed that the expressions of NMDA receptor subunit NR2A increased at 6 h, and reached the peak at 72 h, and returned to normal point at day 5 after operation in ICH group and TM group. TM inhibitor argatroban reduced the expression of NMDA receptor subunit NR2A at 72 h post-operation, which were significant different from that in TM group(P<0.05). Argatroban significantly reduced the permeability of BBB and the water content of brain(P<0.05). Conclusion NMDA receptor subunit NR2A played an important role in brain injury after ICH. Thrombin induced brain injury by activating NMDA receptor subunit NR2A and up-regulating its expression. Argatroban can attenuate hemorrhagic brain injury by inhibiting NMDA receptor subunit NR2A expression.

关 键 词：NMDA受体 亚单位NR2A 凝血酶 脑出血 阿加曲班 

分 类 号：R743.3[医药卫生—神经病学与精神病学]