消退素E1对内毒素血症心肌损伤的保护作用及机制研究

Protective effect and mechanism of resolvin E1 on myocardial injury induced by endotoxemia

目的:探讨消退素E1对内毒素血症心肌损伤的保护作用及机制研究。方法:选择SPF级C57BL/6雄性小鼠40只,随机分成为四组:正常组、对照组、模型组和药物组,通过腹腔注射25 mg/kg脂多糖(LPS)构建内毒素血症模型。其中,模型组和药物组小鼠腹腔注射25 mg/kg的LPS,正常组和对照组小鼠注射等量0.9%氯化钠液。对照组和药物组小鼠按5 mg/kg灌胃消退素E1,正常组和模型组小鼠灌胃等量0.9氯化钠液。超声心动图评估心脏功能,检测小鼠血清乳酸脱氢酶(LDH)、CK-MB、cTnI、IL-1、IL-6、IL-18和TNF-α水平。免疫荧光染色检测心脏组织Ly6G+和F4/80+阳性细胞表达。结果:超声结果显示:与正常组比较,模型组小鼠LVEDd和LVESd明显升高, EF和缩短分数(FS)明显降低,(P<0.05);与模型组比较,药物组小鼠LVEDd和LVESd明显降低,EF(%)和FS(%)明显升高(P<0.05)。与正常组比较,模型组小鼠心肌损伤标志物LDH、CK-MB和cTnI显著升高(P<0.05);与模型组比较,药物组小鼠LDH、CK-MB和cTnI显著降低(P<0.05)。与正常组比较,模型组小鼠心脏Ly6G+和F4/80+阳性细胞表达显著升高(P<0.05);与模型组比较,药物组小鼠心脏Ly6G+和F4/80+阳性细胞显著降低,差异有统计学意义(P<0.05)。与正常组相比,模型组小鼠血清IL-1、IL-6、IL-18和TNF-α表达明显升高(P<0.05);而与模型组相比,药物组小鼠清IL-1、IL-6、IL-18和TNF-α表达显著降低(P<0.05)。结论:消退素E1可显著降低循环和心脏炎症,改善内毒素血症引起的心肌损伤。

Objective:To investigate the protective effect and mechanism of resolvin E1 on myocardial injury induced by endotoxemia.Methods:Forty male C57BL/6 J mice were randomly divided into four group:normal group,control group,modE1 group and treated group.lipopolysaccharide-base mouse myocardial injury modE1 was to explore the role of Resolvin E1 in vivo.Cardiac function was assessed by echocardiography.In addition,serum levels of lactate dehydrogenase(LDH),creatine kinase isoenzyme(CK-MB),cardiac troponin I(cTnI),IL-l,IL-6,IL-l8 and TNF-a were measured.Ly6G and F4/80 positive cells were detected by immunofluorescence staining.Results:Compared with the normal group,the mice in the modE1 group had significantly higher LVEDd and LVESd,lower EF and FS(P<0.05);compared with the modE1 group,the mice in the drug group had significantly lower LVEDd and LVESd,and higher EF and FS(P<0.05).Compared with the normal group,the levels of LDH,CK-MB and cTnI in the modE1 group were significantly increased(P<0.05),while the levels of LDH,CK-MB and cTnI in the drug group were significantly decreased(P<0.05).Compared with the normal group,Ly6G+and F4/80+positive cells in the heart of mice in the modE1 group were increased(P<0.05);compared with the modE1 group,Ly6G+and F4/80+positive cells in the heart of mice in the drug group were decreased(P<0.05).Compared with normal group,serum levels of IL-1,IL-6,IL-18 and TNF-a in modE1 group were significantly increased(P<0.05),while serum levels of IL-1,IL-6,IL-18 and TNF-a in the drug group were significantly decreased(P<0.05).Conclusions:Resolvin E1 can signif­icantly reduce the inflammatory response in circulatory and cardiac,and then improve myocardial injury induced by endotoxemia.