p38MAPK信号通路在瑞芬太尼或缺血预处理减轻大鼠肝缺血再灌注损伤中的作用  

Role of p38MAPK pathway in protective effect of remifentanil or ischemic preconditioning against hepatic ischemia-reperfusion injury in rats

作　　者：赵鸽[1] 陈正春 申新[1] 陈亚丽[1] 吕毅[1] 

机构地区：[1]西安交通大学医学院第一附属医院麻醉科,西安市710061 [2]陕西省山阳县人民医院麻醉科

出　　处：《中华麻醉学杂志》2012年第1期99-102,共4页Chinese Journal of Anesthesiology

基　　金：陕西省自然科学基金（SJ08C213）

摘　　要：目的评价p38丝裂原蛋白激酶（p38MAPK）信号通路在瑞芬太尼或缺血预处理减轻大鼠肝缺血再灌注损伤中的作用。方法健康SD大鼠144只，雌雄不拘，体重200～250g，采用随机数字表法，将其随机分为6组（n=24）：假手术组（S组）；肝缺血再灌注组（I／R组）采用动脉夹夹闭左叶和中叶肝蒂30min，恢复灌注的方法制备大鼠肝缺血再灌注模型；瑞芬太尼组（R组）于缺血前30min静脉输注瑞芬太尼2μg·kg^-1·min^-1至再灌注120min；缺血预处理组（IPC组）于缺血前30min行缺血5min，再灌注5min，重复3次后制备缺血再灌注模型；SB＋R组和sB＋IPC组分别于输注瑞芬太尼或缺血预处理前5min静脉注射p38mAPK特异性抑制剂SB2035800．2mg／kg，其余组给予等体积生理盐水。于再灌注30、60、90和120min时各组分别随机取6只大鼠抽取肝下腔静脉血测定血清ALT和AST活性；采用ELISA法测定TNF—α及IL-1β浓度；随后处死大鼠，取肝组织，采用Western blot法测定磷酸化p38MAPK的表达，观察病理学结果。结果与S组相比，I／R组各时点血清ALT、AST、TNF-α及IL-1β水平升高（P〈0．05），病理学损伤明显加重；与I／R组相比，RPC组和IPC组血清A岍和AST活性、TNF-α及IL-1β浓度降低，再灌注90min时磷酸化p38MAPK表达上调（P〈0．05），sB＋RPC组和sB＋IPC组各指标差异无统计学意义（P〉0．05）；SB＋RPC组与RPC组，sB＋IPC组和IPC组相比，血清ALT、AST、TNF-α及IL-1β水平升高，再灌注90min时磷酸化p38MAPK表达下调（P〈0．05），病理学损伤明显加重。结论瑞芬太尼和缺血预处理可减轻大鼠肝缺血再灌注损伤，其机制可能与激活p38MAPK信号通路抑制炎性反应有关。Objective To investigate the role of p38 mitogen-activated protein kinase （p38MAPK） pathway in the protective effect of remifentanil or ischemic preconditioning （IPC） against hepatic ischemia-reperfusion （I/R） injury in rats. Methods One hundred and forty-four male SD rats, weighing 200-250 g, were randomly assigned into 6 group （ n = 24 each） ： sham operation group （group S）, I/R group, remifentanil group （group R）, IPC group, SB203580 （a specific p38MAPK inhibitor） ＋ remifentanil group （group SB ＋ R）, and SB ＋ IPC group. The animals were anesthetized with intraperitoneal 20% urethane 1 mg/kg. Partial liver ischemia was pro- duced by clamping the hepatic pedicle supplying left lobe and middle lobe for 30 rain, followed by 120 rain Ieperfusion. In group R, remifentanil was infused intravenously at 2μg· kg^- 1 . min^- 1 starting from 30 min before ischemia until the end of reperfusion. In IPC group, the rats were subjected to 3 episodes of 5 min ischemia at 5 min intervals before I/R. SB203580 0.2 mg/kg was injected intravenously at 5 min before remifentanil infusion or IPC in groups SB ＋ R and SB ＋ IPC, and the equal volume of normal saline was given in the other groups. Six rats in each group were selected at 30, 60, 90 and 120 min of reperfusion and venous blood samples were taken from inferior vena cava for measurement of serum ALT and AST activities and concentrations of TNF-α and IL-1β. The rats were then sacrificed and liver tissues were taken for microscopic examination and determination of phosphor-p38MAPK expression by Western blot. Results Compared with group S, sermn AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased at each time point （ P 〈 0.05） and pathological injury was aggravated in group I/R. Compared with group I/R, serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly decreased and phosphor-p38MAPK expression was up-regulated at 90 min of reperfusion in groups R and IPC

关 键 词：P38丝裂原活化蛋白激酶 哌啶类 缺血预处理 再灌注损伤 肝 

分 类 号：R614[医药卫生—麻醉学]