卡马西平保护小鼠肝脏缺血再灌注损伤  

Carbamazepine protects the liver against ischemia/reperfusion injury in mice

作　　者：雷延昌[1] 罗盼[1] 李雯[1] 

机构地区：[1]南昌大学附属感染病医院,江西省南昌市330006

出　　处：《世界华人消化杂志》2013年第33期3617-3622,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81160065~~

摘　　要：目的:了解卡马西平对肝脏缺血再灌注的保护作用.方法:动脉夹阻断肝脏血流1 h释放形成再灌建立小鼠肝脏缺血再灌注模型.6-8周龄♂B a l b/c随机分为缺血再灌组(对照组)、卡马西平组、卡马西平+氯喹组,每组6只.生化检测各组缺血再灌不同时间点血清丙氨酸转氨酶(alanine aminotransferase,ALT)和谷草转氨酶(aspartate transaminase,AST)水平.HE染色观察肝脏形态学变化,免疫组织化学分析肝脏高迁移率族蛋白B1(high mobility group box1,HMGB1)表达,免疫印迹检测Caspase3、Atg7、Beclin-1和微管相关蛋白1轻链3Ⅱ(light chain 3Ⅱ,LC3Ⅱ)表达.结果:卡马西平阻止缺血再灌注小鼠肝脏LC3Ⅱ和自噬相关基因Atg7与Beclin-1的表达下降.卡马西平组缺血再灌后2、6和12 h血清ALT/AST水平显著低于缺血再灌组(P<0.01).卡马西平降低缺血再灌6 h肝细胞Caspase3表达和HMGB1胞浆移位.抑制自噬的药物氯喹具有对抗卡马西平降低Caspase3表达、HMGB1胞浆移位和血清ALT/AST水平的效应.结论:卡马西平通过促进肝细胞自噬保护肝脏缺血后再灌注损伤.AIM： To explore the effects of carbamazepine （CBZ） on hepatic ischemia/reperfusion （I/R） injury in mice. METHODS： Hepatic ischemia in male Balb/c mice was induced by occluding the portal triad for 1 h, and reperfusion was initiated by remov- ing a microvascular clamp. Mice were randomly assigned to three groups （n= 6 for each group）： I/R group as control, CBZ treatment group, and CBZ plus chloroquine （CQ） group. Serum ALT/ AST levels at different time points were measured using biochemical methods. Hepatic morphologi- cal changes at 6 h after I/R were assessed by HE staining, and hepatocyte high mobility group box 1 （HMGB1） cytoplasmic translocation was de- tected by immunohistochemistry. Expression of Caspase3, Atg7, Beclin-1 and light chain 3 Ⅱ （LC3 Ⅱ ） in liver tissue was analyzed by Western blot.RESULTS： CBZ blocked the depletion of Atg7 and Beclin-1 and LC3II expression after reperfu- sion. CBZ treatment decreased ALT/AST levels significantly 2, 6 and 12 h after I/R compared with the I/R group （all P 〈 0.01）. Expression of Caspase3 in liver tissue and hepatocyte HMGB1 cytoplasmic translocation at 6 h after I/R were also decreased significantly in the CBZ group （both P 〈 0.01）. CQ antagonized the effect of CBZ in decreasing ALT/AST levels, Caspase3 expression and hepatocyte HMGB1 cytoplasmic translocation.CONCLUSION： CBZ protects the liver against I/R injury in mice.

关 键 词：卡马西平 缺血再灌注 自噬 高迁移率族蛋白B1胞浆移位 

分 类 号：R965[医药卫生—药理学]