δ阿片受体激动剂对脓毒症大鼠肝线粒体呼吸功能的保护作用

Protective effect of δ opioid receptor agonist on mitochondrial respiratory function in a rat model of sepsis

目的探讨δ阿片受体激动剂DADLE(D-Ala2-D-Leu5-enkephalin)对脓毒症大鼠肝线粒体呼吸功能的保护作用。方法将60只健康雄性SD大鼠随机分为脓毒症组(SEP组,n=20)、假手术组(SO组,n=20)和DADLE组(n=20)。采用改良盲肠结扎穿孔方法建立脓毒症大鼠模型,假手术组除不结扎刺穿盲肠,DADLE组建立模型后按5 m L/kg剂量腹腔注射浓度为0.5 mg/m L的DALDE。制模8 h后处死大鼠,取血清检测ALT和AST水平,取肝组织测定肝细胞线粒体呼吸功能及肝组织ATP、ADP、AMP含量。结果 DADLE组大鼠呼吸控制率(RCR)、磷/氧化(ADP/O)与SEP组比较显著升高(P<0.05),DADLE组肝脏ATP含量明显高于SEP组(P<0.05)。DADLE组与SEP组比较血ALT和AST水平明显降低(P<0.05)。结论 DADLE对脓毒症大鼠肝脏线粒体呼吸功能具有保护作用,可改善肝细胞能量代谢。

Objective To study the protective effect of δ opioid receptor agonist DADLE（D-Ala2-D-Leu5-enkephalin） on mitochondrial respiratory function in a rat model of sepsis. Methods Sixty SD rats were randomly divided in to sham operated group （SO）, septic group （SEP）, and DADLE group （DADLE）, each of 20 cases. 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 intra-peritoneal injection after CLP. All rats were sacrificed 8 hours after CLP. ALT and AST in blood were determined. Mitochondrial respiratory function was evaluated by the clark oxygen eletrode. The levels of ATP, ADP, AMP were determined by high performance liquid chromatogra phy （HPLC）. Results RCR and ADP/O in DADLE group were much higher than that in SEP group （P〈0.05）. ATP in DADLE groups were much higher than SEP group （P〈0.05）, while ALT and AST of DADLE group were significantly lower than SEP group （P〈0.05）. Conclusion DADLE can protect mitochondrial respiratory function and improve the hepatocellular energy metabolism in sepsis.