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δ阿片受体激动剂对脓毒症大鼠肝脏保护作用的研究
Hepatoprotective effect of DADLE in rat with sepsis
【摘要】 目的探讨δ阿片受体激动剂DADLE(D-Ala2-D-Leu5-enkephali)对脓毒症大鼠肝脏的保护作用。方法SD大鼠60只,分为假手术组(SO组)、脓毒症组(SEP组)和DADLE(5mg/kg)给药处理组(DADLE组),每组20只。采用改良盲肠结扎穿孔方法(CLP)建立大鼠脓毒症模型,SO组除不结扎刺穿盲肠外,其余操作同SEP组,DADLE组模型建立后立即按5ml/kg剂量静脉注射浓度为0.5mg/ml的DADLE。制模8h后处死大鼠,取血检测ALT和AST水平。采用Clark氧电极技术测定肝细胞线粒体呼吸功能,高效液相色谱法测定肝组织ATP、ADP、AMP含量。观察各组大鼠肝组织病理形态改变。结果与SO组比较其余两组ALT和AST明显升高,而DADLE组与SEP组比有明显降低(P<0.05)。给予DADLE治疗的大鼠呼吸控制率(RCR)、磷/氧化(ADP/O)与SEP组比较显著升高(P<0.05)。组织病理学提示DADLE组大鼠肝脏组织坏死灶及炎细胞浸润明显轻于SEP组。结论δ阿片受体激动剂DADLE对脓毒症大鼠肝脏具有一定的保护作用,其机制可能与保护线粒体呼吸功能,减轻线粒体水肿,改善肝细胞能量代谢有关。
【Abstract】 Objective To study the hepatoprotective effect of DADLE(D-Ala2-D-Leu5-enkephali) in rat with sepsis.Methods Sixty SD rats were randomly divided in to sham operated group (SO),septic group(SEP),and DADLE group (DADLE).Sepsis model was produced by cecal ligation and puncture (CLP).In SO group,the abdomen was opened without any other treatment.In DADLE group,DADLE(0.5 mg/ml) was administer at a dose of 5 ml/kg by intravenous injection after CLP.All rats were sacrificed 8 h after CLP.ALT and AST in blood were determined.The function of mitochodria was evaluated by the clark oxygen eletrode.The levels of ATP,ADP,AMP were determined by high performance liquid chromatography (HPLC).The changes of mitochondrial ultrastructure were observed by using electron microscope.Results ALT and AST of DADLE groups were significantly lower than SEP group(P<0.05),while RCR and ADP/O were much higher than SEP group(P<0.05).ATP of DADLE groups were much higher than sep group(P<0.05).The damage of hepatocellular mitochondrial structure and function of SEP group were much severe than DADLE groups.Conclusions DADLE has hepatoprotective effect in rats with sepsis.
【Key words】 Sepsis; Enkephalin,leucine-2-alanine; Disease models,animal; Adenosine triphosphate; Mitochondria,liver;
- 【文献出处】 中华临床医师杂志(电子版) ,Chinese Journal of Clinicians(Electronic Edition) , 编辑部邮箱 ,2009年07期
- 【分类号】R96
- 【被引频次】3
- 【下载频次】77