NMDA受体NR2A亚单位在凝血酶诱导的大鼠脑出血后脑损伤作用机制的研究  

Mechanism of NMDA receptor NR2A subunit in thrombin-induced brain injury after experimental intracerebral hemorrhage in rats

作　　者：侯玉超[1] 沈霞[1] 吴保鑫 孙秀娟[1] 花放[1] 叶新春[1] 齐素华[3] 崔桂云[1] 

机构地区：[1]徐州医学院附属医院神经内科,徐州2210022 [2]江苏沛县人民医院神经内科,沛县221600 [3]徐州医学院生物化学教研室,徐州221004

出　　处：《中国实用神经疾病杂志》2013年第8期1-4,共4页Chinese Journal of Practical Nervous Diseases

基　　金：国家自然科学基金(81271344)

摘　　要：目的探讨N-甲基-D天冬氨酸受体(NMDA)受体NR2A亚单位在凝血酶诱导的大鼠脑出血后脑损伤中的作用机制。方法将健康雄性SD大鼠随机分为生理盐水对照组、凝血酶组、凝血酶+阿加曲班组,建立大鼠脑出血模型。造模后48h,采用伊文思蓝法检测血脑屏障(BBB)的通透性,干-湿重法测脑组织的含水量。采用Western-blot方法观察出血后各时间点(0h、0.5h、6h、24h、72h、120h)血肿周围脑组织NR2A分布及动态变化规律。结果 (1)阿加曲班可以明显改善大鼠脑出血BBB通透性(P<0.05),血肿周围脑水肿明显减轻(P<0.05)。(2)Western-blot结果显示,NR2A在6h时开始增加,72h达到高峰,在120h时基本恢复。阿加曲班可以明显减少NR2A在72h时的表达(P<0.05)。结论 (1)NR2A参与了凝血酶诱导的脑出血后脑损伤的病理生理过程。(2)凝血酶可能通过上调NR2A表达引起脑出血后脑组织的损伤。Objective To investigate the mechanism of action of NMDA receptor NR2A subunit in the brain damage fol- lowing thrombin-induced intracranial hemorrhage in rats. Methods Healthy male SD rats were randomly allocated into three groups： control, thrombin （TM） and argatroban （ARG） intervention groups to establish the rat model. The dye Evans blue assay was used to detect the blood brain barrier （BBB） permeability, the dry-wet method was used to measure the brain water content 48 hours after the modeling. The distribution and dynamic rule of NR2A were measured by Western bolt at times（0 h, 0.5 h, 12 h, 72 h, 120 h）in TM group. Results ARG reduced the permeability of BBB significantly（P〈0.05）, and decreased water content of brain significantly（P〈0.05）. The result of Western-blot analysis showed that the expressions of NR2A began at 6-hour, and reached the peak at 72-hour, and reached the normal point at 120-hour after modeling in TM group. ARG sig- nificantly reduced NR2A expressions at 72-hour （P〈0.05）. Conclusion NR2A playes an important role in brain injury after thrombin-induces intracranial hemorrhage in rats. Thrombin induced brain injury by activating NR2A and promoting its expres- sion.

关 键 词：NMDA受体 NR2A亚单位 凝血酶 脑出血 阿加曲班 

分 类 号：R743.34[医药卫生—神经病学与精神病学]