大鼠肝缺血-再灌流损伤脑组织p38MAPK与脑细胞凋亡的关系  

The relationship of neuronal apoptosis and cerebral p38MAKP following liver ischemia-reperfusion iniury in rats

作　　者：王旭林[1] 王红梅[2] 蔡善荣[1] 姜强[1] 徐文鸿[1] 张苏展[1] 

机构地区：[1]浙江大学医学院附属第二医院肿瘤研究所,杭州310009 [2]新疆医科大学基础医学院病理生理教研室

出　　处：《中华急诊医学杂志》2006年第5期410-414,共5页Chinese Journal of Emergency Medicine

摘　　要：目的观察肝缺血-再灌流损伤过程中大脑皮质层p38有丝分裂素激活蛋白激酶(p38MAPK) 的变化和神经元凋亡,以探讨p38 MAPK与脑组织神经元凋亡的关系。方法建立肝缺血-再灌流损伤动物模型,分为对照组、缺血30 min组(I组)、缺血30 min再灌流组(I／R组)、缺血30 min再灌流后1 h组(I/ R 1h)、缺血30 min再灌流后2 h组(I／R 2h)、缺血30 min再灌流后4 h组(I/R 4h)。应用免疫组化法测定各组肝组织中iNOS的变化和脑皮质层p38MAPK的改变,应用原位细胞凋亡法测定神经元凋亡,同时观察肝和脑组织病理学改变。结果肝缺血-再灌流损伤形成过程中,随着再灌流时间延长肝组织出现iNOS的高表达,同时大脑皮层出现p38MAPK改变和神经元凋亡。肝组织iNOS与p38MAKP呈正相关(r=0．91,P <0．05)。p38MAPK的表达与phospho-p38MAPK的表达呈正相关(r=0．89,P<0．05),phospho-p38MAPK的表达与凋亡指数呈正相关(r=0．95,P<0．05)。HE染色见肝细胞水肿,炎性细胞浸润,甚至细胞坏死。脑皮质层见神经元水肿、坏死。结论肝缺血-再灌流损伤可导致大脑结构和功能的改变。损伤过程中产生 iNOS作为炎性细胞因子导致大脑皮层p38MAKP的改变,从而引起神经元凋亡。Objective To observe the changes of p38MAPK and apoptosis index in cerebral cortex following liver ischemia-reperfusion injury, and to evaluate the effect of p38MAPK on neuronal apoptosis. Methods A model of liver ischemia-reperfusion injury was established. The contents of p38MAPK in cortex regions and the changes of iNOS in the liver tissue were measured by immunohistochemical technique. Neuronal apoptosis was detected by TUNEL in sham operation （control group）, at 30 minutes after ischemia without reperfusion （group 1）, reperfusion following ischemia 30 minutes （group I/R）, 1 hour reperfusion following ischemia 30 minutes （group 1/R 1h）, 2 hour reperfusion following ischemia 30 minutes （group I/R 2h）, and 4 hours reperfusion following ischemia 30 minutes （group I/R 4h）. Results There were obvious changes of p38MAPK and neuronal apoptosis, iNOS was highly expressed in the liver tissue, especially with prolonged liver ischemia-reperfusion injury. There were positive correlations between iNOS and p38MAPK, between p38MAPK and phospho-p38MAPK, between photo-p38MAPK and apoptosis index. Eedma and infdtration of inflammatory cells, in liver tissues, as well as nacrosis, were detected by HE-staining. Conclusion Liver ischemia-reperfusion injury could cause the change of brain structure and function, and iNOS derived. As an inflammatory mediator, iNOS could lead to the increase of p38MAPK and neuronal apoptosis.

关 键 词：肝缺血-再灌流损伤 大脑 凋亡 

分 类 号：R363[医药卫生—病理学]