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瑞芬太尼预处理对大鼠肝缺血再灌注损伤的保护作用
孙玉明1△,葛彦虎1,2△,杨立群1*,吕浩1,刘艳涛1,俞卫锋1
0
(1.第二军医大学东方肝胆外科医院麻醉科,上海 200438;2.解放军总医院第309临床部麻醉科,北京 100091)
摘要:
目的:探讨瑞芬太尼预处理对大鼠肝脏缺血再灌注损伤的保护作用。方法:用SD大鼠制作肝脏缺血再灌注模型,随机分为缺血再灌注组(I/R) 、缺血预处理组(IPC)、瑞芬太尼预处理组(RPC)和假手术组(Sham),其中RPC组又分0.2、1、10 μg·kg-1·min-1共3个剂量亚组(RPC1、RPC2、RPC3)。观察各组肝脏缺血45 min再灌注2 h后血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,肝细胞匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)含量及肝组织病理学的改变。并用TUNEL染色比较各组肝细胞凋亡情况。结果:I/R组、RPC1组肝脏缺血再灌注后血清ALT、AST 含量显著升高,肝细胞匀浆中MDA含量增高,SOD含量降低,肝组织病理学损害明显增加;TUNEL染色显示存在大量凋亡细胞。而IPC、RPC2、RPC3组肝脏缺血再灌注后血清ALT 和AST 含量与前二组相比显著降低,肝细胞匀浆中MDA含量减少,SOD含量增加,肝组织病理学损害和凋亡明显减轻;TUNEL染色显示凋亡细胞明显少于前两组。Sham组未见明显酶学改变和病理学损害表现。结论:合适剂量的瑞芬太尼预处理对肝脏缺血再灌注损伤有类似IPC的保护作用。
关键词:    再灌注损伤;瑞芬太尼;缺血预处理
DOI:10.3724/SP.J.1008.2009.0659
投稿时间:2008-07-21修订日期:2009-04-22
基金项目:国家自然科学基金(30600584),上海市科技启明星计划(08QA14007).
Remifentanil preconditioning attenuates hepatic ischemia and reperfusion injury in rats
SUN Yu-ming1△,GE Yan-hu1,2△,YANG Li-qun1*,L Hao1,LIU Yan-tao1,YU Wei-feng1
(1.Department of Anesthesiology,Eastern Hepatobiliary Hospital,Second Military Medical University,Shanghai 200438,China;2.Department of Anesthesiology,No.309 Clinical Division,PLA General Hospital,Beijing 100091)
Abstract:
Objective:To investigate the protective effect of remifentanil preconditioning on liver ischemia and reperfusion injury in rats.Methods:Forty-eight healthy adult SD rats,weighing 200-300 g,were divided into 4 groups:ischemic reperfusion group(I/R),ischemic preconditioning group(IPC),sham operation group(Sham),and remifentanil preconditioning group(RPC).The RPC group was further subdivided into 3 subgroups according to the dose of remifentanil:0.2 μg·kg-1·min-1(RPC1 group),1 μg·kg-1·min-1(RPC2 group ),and 10 μg·kg-1·min-1(RPC3 group).All rats except for those in the sham group were subjected to ischemia for 45 min and followed by reperfusion for 2 hours.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST) and liver homogenate levels of MDA,SOD were determined.H-E staining was used to observe the hepatic histopathological changes and TUNEL staining was used to examine hepatocyte apoptosis.Results:In I/R and RPC1 group,serum ALT and AST were significantly increased; hepatic homogenate MDA content was increased and SOD content was decreased,accompanied by aggravated pathological injury; TUNEL staining showed large amount of apoptotic cells.Compared with I/R and RPC1 groups,serum ALT and AST levels in IPC,RPC2,and RPC3 groups were significantly decreased after liver ischemia and reperfusion,accompanied by decreased homogenate MDA level,increased SOD level,and improved pathological injury.TUNEL staining showed much less apoptotic hepatocytes in IPC,RPC2,and RPC3 groups compared with I/R and RPC1 groups.No obvious changes in histopathology or in other parameters were observed in the sham group.Conclusion:Pre-treatment with remifentanil,like ischemic precondition,can protect liver from ischemia and reperfusion injury.
Key words:  liver  reperfusion injury  remifentanil  ischemic precondition