鞣花酸灌胃对脂多糖诱导的脓毒症心功能不全的影响

Effects of Ellagic Acid Intragastric Administration on Cardiac Insufficiency Induced by Lipopolysaccharide Sepsis

目的探究鞣花酸(EA)对脂多糖(LPS)诱导的脓毒症所致心功能不全保护作用的潜在机制。方法将32只C57BL/6小鼠分为4组:对照Control(Con)组(n=8),LPS组(n=8),20EA(20 mg/kg)组(n=8),40EA(40 mg/kg)组(n=8)。20EA及40EA组用EA灌胃14 d后腹腔注射10 mg/kg LPS,Con组使用等量生理盐水灌胃。超声心动图评测心功能,分析射血分数及短轴缩短率,生化法检测超氧化物岐化酶(SOD)、丙二醛(MDA)、肌酸激酶同工酶(CK-MB)及乳酸脱氢酶(LDH)血清水平。结果超声心动图显示EA以剂量依赖的方式改善LPS诱导的心脏的射血分数及短轴缩短率。生化检测显示,与对照组相比,LPS组SOD血清水平下降,MDA、CK-MB及LDH血清水平升高,EA可呈剂量依赖性上调SOD,下调MDA、CK-MB及LDH的血清水平。蛋白免疫印迹显示EA预处理可上调核转录因子红系2相关因子2(Nrf2)以及血红素加氧酶1(HO-1)的水平。结论EA可有效改善LPS诱导的心功能不全,可能是通过减轻氧化应激水平及上调Nrf2/HO-1水平发挥作用。

Objective To investigate the probable mechanism of ellagic acid(EA)’s preventive effect on cardiac insufficiency caused by lipopolysaccharide(LPS)-induced sepsis.Methods 32 C57BL/6 mice were placed into four groups:Control(Con,n=8),LPS(n=8),20EA(n=8),and 40EA(n=8).20EA and 40EA groups were administered EA for 14 days,followed by intraperitoneal injections of 10 mg/kg LPS.The Con group was given the equivalent saline by gastric gavage.The heart function was evaluated using echocardiography,ejection fraction and fractional shortening were assessed,and serum levels of superoxide dismutase(SOD),malondialdehyde(MDA),creatine kinase isoenzyme(CK-MB),and lactate dehydrogenase(LDH)were tested using a biochemical approach.Results Echocardiography showed that EA improved LPS-induced cardiac ejection fraction and fractional shortening in a dose-dependent manner.Biochemical assays showed that compared with the control group,levels of SOD decreased and serum levels of MDA,CK-MB and LDH increased in the LPS group.EA improved SOD and decreased the serum levels of MDA,CK-MB and LDH in a dose-dependent way.The western blot results indicate that EA pretreatment could increase nuclear factor erythroid 2-related factor 2(Nrf2)and hemeoxygenase-1(HO-1)levels.Conclusion EA can significantly ameliorate the cardiac dysfunction generated by LPS,which may play a role in reducing the level of oxidative stress and elevating the levels of Nrf2/HO-1.