外源性一氧化碳释放分子2对脓毒症小鼠肝脏能量代谢的调控作用及机制

Effect of CORM-2 on liver energy metabolism in sepsis and the potential mechanisms

目的:观察脓毒症小鼠肝脏能量代谢的变化,同时探讨外源性一氧化碳释放分子2(carbon monoxide-releasing molecules-2,CORM-2)对其调控及作用机制。方法:将48只C57BL/6小鼠随机均分成对照组,盲肠结扎穿孔(CLP)组,CORM-2组,无活性CORM-2(inactivated CORM-2,iCORM-2)组。采用CLP术制作脓毒症模型,对照组不作任何处理,CORM-2组和iCORM-2组除术后使用CORM-2或无活性CORM-2外,其余处理同CLP组,术后72 h内连续监测各组12只小鼠血糖浓度的动态变化及存活情况。另选32只小鼠分组同上,术后24 h收集肝脏组织及血浆,检测肝组织的18F-FDG分布、葡萄糖激酶活性、乳酸含量,全自动生化分析仪检测血浆丙氨酸转氨酶(ALT),天冬氨酸转氨酶(AST)。结果:与对照组比较,CLP组葡萄糖代谢水平增强,葡萄糖激酶、AST、ALT活性以及乳酸含量均明显增高(P均<0.05);CORM-2干预后上述指标明显降低(P均<0.05)。与对照组比较,各手术组小鼠血糖在术后36 h内持续下降,且组间差异无统计学意义。结论:CORM-2能明显减少脓毒症小鼠肝18F-FDG摄取、葡萄糖激酶活性和乳酸含量,从而改善脓毒症小鼠肝脏能量代谢紊乱,提高生存率。

Objective： To explore the effects of CO-releasing molecules [ tricarbonyl dichlororutheoium （ Ⅱ ）dimer, CORM-21-liberated CO on liver energy metabolism of septic model and potential mechanisms. Methods： Forty-eight mice were randomly divided into four groups：control group, CLP group, CORM-2 group, inactivated CORM-2（iCORM group）, cecal ligation and puncture （CLP） group. The CORM-2 and iCORM-2 group were treated with CLP surgery then followed by tail vein injection of 8 mg/kg CORM-2 and iCORM-2, respectively. Twelve mice in each group were used during the experiments of blood glucose testing and survival rate measurement. In the other experiment, eight mice were used in each group. Levels of aminotransferases （ALT and AST） were measured by biochemical methods. Glucokinase activity and the concentration of lactate in tissue homogenates were assessed using assay kits. Blood glucose of mice in each groups was tested every 2 hours within 36 hours using a fast blood glucose test meter. A γ counter was used to detect the biodistribution of ^18F-FDG in the liver of mice. Results： The survival rate of septic mice was significantly increased by CORM-2. The uptake of ^18F-FDG was decreased when treated with CORM-2. The activity of glucokinase, AST, ALT and concentration of lactate in septic mice treated with CORM2 were maintained in normal levels. The blood glucose of septic mice was decreased significantly in all the three operation groups. Conclusion： CORM-2-released CO improves the survival of septic mice by modulating the metabolism of glucose septic mice and protecting the function of liver in sepsis mice.