不同剂量磷酸肌酸钠预先给药对大鼠肝缺血再灌注损伤的影响  

Effects of pretreatment with different doses of phosphocreatine on hepatic ischemia-reperfusion injury in rats

作　　者：邹宏运[1] 李元海[1] 张海涅[1] 邬微微[1] 陈珂[1] 

机构地区：[1]安徽医科大学第一附属医院麻醉科,合肥市230022

出　　处：《中华麻醉学杂志》2013年第5期619-621,共3页Chinese Journal of Anesthesiology

基　　金：安徽省教育厅重点项目（KJ2009A058Z）

摘　　要：目的评价不同剂量磷酸肌酸钠预先给药对大鼠肝缺血再灌注损伤的影响。方法健康雄性SD大鼠30只，体重200～250g，采用随机数字表法分为5组（n=6）：假手术组（s组）、缺血再灌注组（I／R组）、不同剂量磷酸肌酸钠预先给药组（P1-3组）。采用阻断肝左中动脉及其门静脉90min恢复灌注的方法制备大鼠肝缺血再灌注模型。P1-3组于缺血前60min时分别尾静脉注射磷酸肌酸钠50、150和450mg／kg。S组和I／R组给予等容量生理盐水。于再灌注4h时采集腹主动脉血样，测定血浆ALT、AST、TNF—α和IL-1β水平。取肝组织，采用ELISA法检测MPO活性，免疫组化法检测细胞间粘附分子（ICAM-1）的表达水平，TUNEL法检测肝细胞凋亡数，电镜下观察病理学结果。结果与s组比较，I／R组和P1-3组肝组织MPO、血浆ALT、AST活性及TNF-α、IL-1β浓度、肝细胞凋亡数升高（P〈0．05）；与I／R组比较，P1-3组上述指标降低（P〈0．05）；P1-3组上述指标依次降低（P〈0．05）。结论磷酸肌酸钠预先给药可呈剂量依赖性地减轻大鼠肝缺血再灌注损伤，其机制与抑制炎性反应有关。Objective To evaluate the effects of pretreatment with different doses of phosphocreatine on hepatic ischemia-reperfusion （I/R） injury in rats. Methods Thirty male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into 5 groups （ n = 6 each） ： sham operation group （group S）, hepatic I/R group （group I/R）, and pretreatment with different doses of phosphocreatine groups （groups P^-3 ） ~ Hepatic I/R was induced by 90 min occlusion of the hepatic artery and portal vein entering the middle and left lobes of the liver followed by 4 h reperfusion in anesthetized rats. Phosphocreatine 50, 150 and 450 mg/kg were injected via the tail vein at 60 min before ischemia in groups P1-3, respectively. In groups S and I/R, the equal volume of normal saline was given in- stead. Blood samples were taken from the abdominal aorta at 4 h of reperfusion for determination of plasma alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, TNF-α and IL-1β concentrations. The rats were then sacrificed and the livers were removed for determination of myeloperoxidase （MPO） activity （by ELISA）, intercellular adhesion molecule-1 （ICAM- 1 ） expression （by immunohistochemistry）, and cell apoptosis （by TUNEL） and for microscopic examination （by electron microscopy）. Results The MPO activity in liver tissues, plasma ALT and AST activities, TNF-α and IL-1β concentrations and the number of apoptotic cells were significantly higher in groups I/R and Pi-3 than in group S, while lower in groups P1-3 than in group I/R （P 〈 0.05）. The parameters mentioned above were decreased in turn in groups P1-3 （ P 〈0. 05） . Conclusion Phosphocreatine pretreatment can attenuate the hepatic I/R injury in rats in a dose-dependent manner and inhibition of the inflammatory responses is involved in the mechanism.

关 键 词：磷酸肌酸 再灌注损伤 肝 预先给药 

分 类 号：R[医药卫生]