凝血酶与出血性脑组织损伤的相关性动物实验研究  

Study on role of thrombin in brain damage after intracerebral hemorrhage in rats

作　　者：张琳[1] 姜亚军[2] 吴灏昕[3] 

机构地区：[1]东南大学附属中大医院神经内科,江苏南京210009 [2]江苏省中医院脑病中心,江苏南京210029 [3]南京中医药大学中医基础理论教研室,江苏南京210029

出　　处：《现代医学》2005年第4期216-219,共4页Modern Medical Journal

基　　金：国家自然基金资助项目(30171166)

摘　　要：目的观察大鼠脑内注入凝血酶或全血后神经细胞凋亡和脑组织水肿的动态改变,并观察凝血酶特异性抑制剂(水蛭素)能否减轻凝血酶对脑组织的损伤。方法成年168只SD大鼠随机分为5组,即凝血酶组、脑出血组、凝血酶加水蛭素组、脑出血加水蛭素组和生理盐水对照组,分别向大鼠右侧基底节区注入凝血酶、全血、凝血酶加水蛭素、全血加水蛭素和生理盐水,于注射后62、47、2 h,7 d取脑组织,检测脑组织水含量(干湿重法)、神经细胞的凋亡情况(Tunel法)。结果与生理盐水对照组比较,凝血酶组和脑出血组的脑组织水含量及凋亡细胞数明显增加。时效学研究显示脑出血组脑组织水肿和神经细胞凋亡开始于术后6 h,72 h达高峰,7 d后下降;凝血酶组开始于术后6 h,24 h达高峰,72 h下降。与生理盐水对照组比较,脑出血组术后6 h凋亡细胞数无统计学差异(P>0.05),凝血酶组注入凝血酶后6 h凋亡细胞数有明显增加(P<0.05)。水蛭素干预后脑出血组和凝血酶组的脑组织水含量和神经细胞凋亡数明显降低(P<0.05)。结论大剂量凝血酶诱导的组织水肿和细胞凋亡在24 h达高峰,脑出血后组织水肿及细胞凋亡均于72 h达高峰可能与脑出血后凝血酶逐渐由血肿释放有关,水蛭素能显著减轻脑组织水肿和神经细胞凋亡。Objective To investigate the changes of the brain cell apoptosis and brain edema after intracerebral infusion of the whole blood and 5 U thrombin, and the effect of hirudin on the brain damage. Methods The adult rats were divided into five groups, and intracerebrally given with thrombin solution autologous blood, thrombin solution plus hirudin solution and autologous blood plus hirudin solution or normal saline（, N~） respectively. Alter O, 24,72 hours and 7 days jection, the brains were taken out to detect the cell apoptosis（Tunel method）and the water content of brains. Results The apoptosic cells and brain water contents increased at 6 h after intracerebral hemorrhage （ICH）, peaked at 72 h and decreased on 7 d after ICH, whereas those were increased at 6 h, peaked at 24 h and decreased at 72 h after intracerebral infusion of thrombin. Compared with NS group, the number of apoptosic cells at 6 h after ICH, did not markedly increase（ P 〉 0.05）. However, apoptosic cells and brain water contents were markedly inhibited by coniecion of hirudin and blood/thrombin （ P 〈 0.05）. Conclusion Thrombin possibly induced the brain edema which peaked at 72 h after ICH by gradually realeased from the clot.

关 键 词：凝血酶 脑出血 水蛭素 脑水肿 细胞凋亡 大鼠 

分 类 号：R743.34[医药卫生—神经病学与精神病学]