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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。
Objective To investigate the protective effect of δ opioid receptor agonist DADLE (D-Ala2-D-Leu5-enkephali) on the liver of septic rats. Methods Sixty Sprague-Dawley rats were randomly divided into sham operation group (SO group), sepsis group (SEP group) and DADLE (5 mg / kg) administration group (DADLE group). The model of sepsis was established by modified cecal ligation and puncture (CLP). In SO group, the operation was the same as that of SEP without ligation of the cecum. The model of DADLE group was established by injecting 5ml / kg intravenous injection of 0.5mg / ml of DADLE. Rats were sacrificed 8 h after model establishment. Blood samples were taken for detection of ALT and AST levels. The mitochondrial respiratory function of hepatocytes was measured by Clark oxygen electrode technique. The levels of ATP, ADP and AMP in liver tissue were determined by HPLC. The pathological changes of liver in each group were observed. Results Compared with SO group, ALT and AST in the other two groups were significantly increased, while those in DADLE group and SEP group were significantly lower than those in SO group (P <0.05). Respiratory rate (RCR) and phosphorus / oxidase (ADP / O) in DADLE-treated rats were significantly higher than those in SEP group (P <0.05). Histopathology showed that liver tissue necrosis and inflammatory cell infiltration in DADLE group were significantly lighter than SEP group. Conclusions δ opioid receptor agonist, DADLE, has a protective effect on the liver of septic rats. The mechanism may be related to the protection of mitochondrial respiratory function, mitochondrial edema, and energy metabolism of hepatocytes.