右美托咪定联合缺血预处理对大鼠肝缺血再灌注损伤的作用  

The effect of dexmedetomidine combined with ischemic preconditioning on liver ischemic reperfusion injury in rats

作　　者：郭友祥 邱坤华[1] 张磊[2] 李勇[1] 张加坤[1] 王庭强[1] 欧阳军[2] 

机构地区：[1]中国人民解放军第五四六医院急诊科,新疆维吾尔自治区马兰841700 [2]石河子大学医学院第一附属医院急诊外科,新疆生产建设兵团石河子市832000

出　　处：《中华急诊医学杂志》2016年第9期1142-1148,共7页Chinese Journal of Emergency Medicine

摘　　要：目的探讨右美托咪定联合缺血预处理对大鼠肝缺血-再灌注损伤的作用及可能机制。方法60只健康雄性SD大鼠，体质量（251±18）g，按随机数字表法分为五组（n=12）：假手术组（s组：不阻断入肝血流）、缺血-再灌注组（IR组：缺血30min，再灌注6h）、右美托咪定预处理组（Dex组：右美托咪定25μg/kg于手术30min前腹腔注射）、缺血预处理组（IP组：肝脏续缺血前给予10min缺血和10min再灌注的预处理）和右美托咪定联合缺血预处理组（Dex＋IP组：右美托咪啶25μg／k于手术30min前腹腔注射，且肝脏持续缺血前给予10min缺血和10min再灌注的预处理）。采用Pringle法分别建立大鼠肝脏缺血-再灌注模型，测定肝脏缺血30min再灌注6h后血清中ALT、AST、LDH的浓度。取左侧肝叶组织，通过HE染色观察其病理学改变，TUNEL检测肝脏组织中细胞凋亡数量，免疫组化及Westerenb｜ot测定肝脏组织血红素氧合酶-1的表达，分光光度法检测肝脏组织H：0：、GSH表达。采用SPSS17．0统计软件，多组间比较采用单因素方差分析，两组间比较采用q检验，以P〈0．05为差异有统计学意义。结果与S组相比，其余各组血清中ALT、AST、LDH浓度明显增高（P=0．000）；与IR组相比，Dex组、IP组及Dex＋IP组明显降低（P=0．000）；Dex＋IP组明显低于Dex组及IP组（P=0．000）；AIJT及AST浓度在Dex组与IP组之间差异无统计学意义（P=0．550，0．771），LDH浓度在Dex组明显低于IP组（P=0．000）。肝组织病理学评分及细胞凋亡指数S组最低，IR组最高，Dex组及IP组明显低于IR组（P：0．000），Dex＋IP组明显低于Dex组及IP组（P=0．000），Dex组与IP组之间差异无统计学意义（P=0．704，0．661）。肝组织中血红素氧合酶-1表达S组最低，Dex＋IP组最高，Dex组及IP组低于Dex＋IP组（P=0．000，0．002），IR组低于Dex组及IP组（P=0．000），Dex组及IP�Objective To investigate the effect of dexmedetomidine （Dex） combined with ischemic preconditioning on liver ischemic rcperfusion injury in rats in order to explore its possible mechanism. Methods Sixty healthy male SD rats weighing （251 ± 18 ） g, were randomly （random number） divided into five groups （n = 12 in each）： sham-operation group （Group S： operation without ischemia）, ischemia-reperfusion group （Group IR： hepatic pedicle occlusion for 30 min and reperfusion for 6 h ） , dexmedetomidine preconditioning group （Group Dex： dexmedetomidine 25 μg/kg was given intra- peritoneally at 30 min before operation） , ischemic preconditioning group （Group IP： 10 min ischemia, 10 min reperfusion, followed by hepatic IR） and Dex combined with ischemic preconditioning group （Group Dex ＋ IP： Dex 25μg/kg was given intra-peritoneally at 30 min befor operation, 10 min ischemia and 10 min reperfusion was given followed by hepatic IR）. The hepatic inflow of blood stream was occluded for 30 rain by Pringle maneuver to establish hepatic isehemic reperfusion injury （HIRI） rat model. At the end of reperfusion for 6 h, the concentration of ALT, AST and LDH （ lactate dehydrogenase ） in serum were measured. The liver histological changes were examined after HE staining. The liver cell apoptosis were examined by TUNEL. The expression of heme oxygenase-1 were examined by Westeren blot and immunohistochemistry. H2o2 and GSH （r-glutamylcysteinylglycine） in liver tissue were detected by spectrophotometer. Differences among the groups were analyzed by one-way analysis of variance （ANOVA） and Student-Newman-Keul test by using SPSS version 17.0 software. Differences were considered significant at P 〈 0. 05. Results Serum concentrations of ALT, AST and LDH in group IR, Dex, IP and Dex ＋ IP were significantly higher than those in group S （ P = 0. 000 ）. And those biomarkers in group Dex, IP and Dex ＋ IP, were significantly lower than those in group IR （ P = 0. 000 �

关 键 词：右美托咪定 缺血预处理 肝脏 缺血-再灌注损伤 血红素氧合酶-1 

分 类 号：R614[医药卫生—麻醉学]