紧密连接相关蛋白Claudin-5、ZO-1在大鼠蛛网膜下腔出血后早期脑损伤中的表达及意义  

Expression of Claudin-5 and ZO-1 in Early Brain Injury after Subarachnoid Hemorrhage in Rats

作　　者：陈铎[1] 袁江伟[1] 宋磊[1] 魏翔泰[1] 关俊宏[1] 刘云会[1] 宗志红[2] 

机构地区：[1]中国医科大学附属盛京医院神经外科,沈阳110004 [2]中国医科大学基础医学院生化教研室,沈阳110001

出　　处：《中国医科大学学报》2010年第9期713-716,共4页Journal of China Medical University

基　　金：辽宁省自然科学基金资助项目(20082080);教育部留学归国人员科研启动基金资助项目(2002247)

摘　　要：目的通过观察大鼠蛛网膜下腔出血(SAH)后早期脑皮层紧密连接相关蛋白Claudin-5、ZO-1表达的变化及JNK抑制剂SP600125对其表达的影响,探讨SAH后早期脑损伤的机制。方法成年雄性SD大鼠75只,随机分成假手术组(sham组)、SAH组、SAH+DMSO组、SAH+SP600125(10 mg/kg)组和SAH+SP600125(30 mg/kg)组5组。采用血管内穿刺法建立大鼠SAH模型,在SAH后24 h时,应用电镜观察各组脑皮层微血管血脑屏障形态学变化;应用Western blot检测各组中脑皮层Claudin-5、ZO-1表达的变化。结果 SAH后早期脑皮层微血管发生明显损伤改变;与sham组相比,SAH组出血后24 h Claudin-5、ZO-1的表达水平明显降低(P<0.05),c-Jun氨基端激酶(JNK)抑制剂SP600125明显改善了脑皮层微血管形态学损伤程度,并抑制了Claudin-5、ZO-1表达水平的降低。结论大鼠SAH后早期血脑屏障结构破坏是早期脑损伤关键性机制之一;SP600125可能通过抑制细胞凋亡、保护血脑屏障发挥SAH早期脑损伤的神经保护作用。Objective Aimed to clarify the molecular mechanism after subarachnoid hemorrhage （SAH） by investigating the expression of tight junction protein Claudin-5 and ZO-1 and the effects of SP600125 on them. Methods Seventy-five male Sprague Dawley rats （300 to 350 g） were randomly divided into sham,SAH,SAH ＋ DMSO （dimethyl sufoxide） solution,SAH ＋SP600125 （C-Jun N-terminal kinase inhibitor）10 mg/kg,and SAH ＋SP600125 30 mg/kg groups. The standard endovaseular perforation was performed to produce experimental SAH. The JNK inhibitor SP600125 was intraperitoneally administered at 1 hour before and 6 hours after SAH. Results At 24 hours after SAH,signs of microvessels injury were observed in brain cortex. Compared with the sham group,expression of Claudin-5 and ZO-1 was sig- nificantly decreased （P 〈 0.05 ）. JNK inhibitior SP600125 suppressed the decrease of Claudin-5 and ZO-1 expression, attenuated blood-brain barrier disruption in rats after SAH. Conclusions The blood-brain barrier disruption is an important mechanism of early brain injury after SAH. JNK inhibitor SP600125 improves neurological outcomes and provides neuropmtecfion against acute events after SAH such as bloodbrain barrier disruption and cell apoptosis.

关 键 词：蛛网膜下腔出血 早期脑损伤 紧密连接相关蛋白 血脑屏障 大鼠 

分 类 号：R743.35[医药卫生—神经病学与精神病学]