全肝缺血再灌注对大鼠认知功能的影响  

The Effect on Cognitive Function in Rats with Total Hepatic Ischemia-reperfusion

作　　者：王姬[1] 李真贞[1] 李军祥[1] 左友波[1] 涂发平[1] 

机构地区：[1]川北医学院附属医院麻醉科,四川南充637000

出　　处：《四川医学》2016年第8期845-848,共4页Sichuan Medical Journal

基　　金：四川省卫生和计划生育委员会科研课题(编号:150053)

摘　　要：目的探讨全肝缺血再灌注对大鼠认知功能的影响及机制。方法第一部分,健康雄性成年SD大鼠16只,随机分为两组(n=8):假手术组(S组)和全肝缺血再灌注组(THIR组)。THIR组采用无创血管夹将肝门部的肝动脉、门静脉和胆总管一并夹闭,阻断30 min时开放血流,S组不夹闭肝门部。再灌注24h时取血清及海马,采用ELISA法测定血清及海马中促炎细胞因子TNF-α、IL-6、IL-1β浓度。第二部分,16只SD大鼠进行为期5d的Morris水迷宫定位航行训练,第6天随机分成两组(n=8):假手术组(S组)和全肝缺血再灌注组(THIR组),模型建立方法同前,再灌注24h时进行反向平台实验后处死动物,观察肝及海马HE染色的病理学变化,免疫荧光法检测海马CA1区小胶质细胞标志物离子钙接头蛋白(Iba-1)的表达水平。结果 S组大鼠肝及海马镜下结构未见异常,THIR组再灌注24h时可见明显的肝脏和海马损伤。与S组比较,THIR组再灌注24h时血清和海马TNF-α、IL-6、IL-1β浓度升高,差异有统计学意义(P<0.01),THIR组再灌注24h时大鼠海马CA1区Iba-1阳性细胞数高于S组,差异有统计学意义(P<0.01)。THIR组再灌注24h时大鼠逃避潜伏期、游泳距离增加(P﹤0.05)。结论全肝缺血再灌注导致大鼠认知功能损害,其机制可能与促炎细胞因子释放及脑内海马CA1区小胶质细胞活化有关。Objective To investigate the effect of total hepatic ischemia-reperfusion on cognitive function in rats and its mechanism. Methods The first part：16 male rats, healthy and mature, were randomly divided into two groups （n = 8）：sham operation group （ S） and total hepatic ischemia-reperfusion group （ THIR group） . Noninvasive vascular clamp were taken to make hepatic artery, portal vein and bile duct occlusion together in rats of THIR group and after 30 min, blocked blood flow was opened. S group did not have porta hepatis clamping. After 24h reperfusion, serum and hippocampus were taken to test the con-centration of pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β by ELISA. The second part：16 SD rats were executed a five-day Morris water maze navigation training. On the sixth day, they were randomly divided into two groups （n = 8）：sham operation group （ S） and total hepatic ischemia-reperfusion group （ THIR group） , with the same model as the former. The reverse platform experiment was carried out after 24h reperfusion. Then animals were sacrificed to observe the pathological changes in HE staining of the liver and hippocampus. Using Immunofluorescence to detect the expression levels of microglia marker calcium ion-ized （Iba-1） adapter protein in hippocampal CA1 region. Results Liver and hippocampus of S group rats had no abnormal micro-scopic structures. When after 24h of reperfusion, THIR group rats had significant liver and hippocampus damage. Compared with S group, after 24h of reperfusion, the concentration of TNF-α, IL-6, IL-1β in hippocampus and serum in THIR group were increased（P〈0. 01）, the Iba-1 positive cells in hippocampal CA1 were higher than in S group （P〈0. 01）, the escape latency and swimming distance in THIR group rats increased （ P〈0. 05 ） . Conclusion The total hepatic ischemia and reperfusion in THIR group rats leads to cognitive impairment, which may because of the release of pro-inflammatory cytokines and microglia activation in b

关 键 词：肝 缺血-再灌注损伤 认知 大鼠 

分 类 号：R614[医药卫生—麻醉学]