【摘要】 目的:探究瑞舒伐他汀(RST)抑制JNK1/2的活化对急性心力衰竭(HF)大鼠心脏血流动力学、氧化应激及免疫应答的调节机制。方法:将100只雄性SD大鼠随机选取20只作为健康对照组(Control),80只制成急性HF模型后设为模型组(Cardiac failure)、低浓度RST组(2.5 mg/kg)、中浓度RST组(5 mg/kg)和高浓度RST组(10 mg/kg)。检测各组大鼠平均动脉压(MAP)、左室收缩压(LVSP)及心率(HR);ELISA检测血清中肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、肌红蛋白(Mb)、诱生型一氧化氮合酶(iNOS)和IL-1β水平;试剂盒检测超氧化物歧化酶(SOD)、活性氧(ROS)、丙二醛(MDA)水平;HE染色观察大鼠心肌损伤;免疫组化检测IL-6表达;Western blot检测大鼠心肌细胞中Caspase-3、Caspase-9、JNK1/2蛋白表达情况。结果:相比于健康对照组,模型组大鼠MAP、LVSP、HR、SOD显著降低(P<0.05),CK、Mb、CK-MB、ROS、MDA、IL-1β、iNOS水平、IL-6阳性率、Caspase-3、Caspase-9、p-JNK1/2蛋白表达显著升高(P<0.05),JNK1/2蛋白表达无显著变化(P>0.05);相比于模型组,RST各组MAP、LVSP、HR、SOD水平显著升高(P<0.05),且呈浓度依赖性,CK、Mb、CK-MB、ROS、MDA、IL-1β、iNOS水平、IL-6阳性率、Caspase-3、Caspase-9、p-JNK1/2蛋白表达显著降低(P<0.05),且呈浓度依赖性,JNK1/2蛋白表达无显著变化(P>0.05)。结论:RST可通过抑制JNK1/2的活化调节急性HF大鼠心脏血流动力学及免疫应答并抑制氧化应激反应,且在一定浓度范围内呈浓度依赖性。更多还原

【Abstract】 Objective:To investigate regulation mechanism of rosuvastatin(RST) for cardiac hemodynamics,oxidative stress and immune response in rats with acute heart failure(HF) by inhibiting JNK1/2 activation.Methods:A total of 100 male SD rats were enrolled,20 rats were randomly selected as healthy control group(Control),80 rats were made into acute HF model,and then divided into model group(Cardiac failure),low-concentration RST group(2.5 mg/kg),middle-concentration RST group(5 mg/kg) and high-concentration RST group(10 mg/kg).Mean arterial pressure(MAP),left ventricular systolic pressure(LVSP) level and heart rate(HR) in each group were measured.Levels of serum creatine kinase(CK),creatine kinase isoenzyme(CK-MB),myoglobin(Mb),inducible nitric oxide synthase(iNOS) and IL-1β were detected by ELISA.Levels of superoxide dismutase(SOD),reactive oxygen species(ROS) and malonaldehyde(MDA) were detected by reagent box.Myocardial injuries of rats were observed by HE staining.IL-6 expression was detected by immunohistochemistry.Expressions of Caspase-3,Caspase-9 and JNK1/2 protein in rats cardiomyocytes were detected by Western blot.Results:Compared with healthy control group,MAP,LVSP,HR and SOD in model group were significantly decreased(P<0.05),while CK,Mb,CK-MB,ROS,MDA,IL-1β,iNOS level,positive rate of IL-6,Caspase-3,Caspase-9 and p-JNK1/2 proteins expressions were significantly increased(P<0.05),and there was no significant change in JNK1/2 protein expression(P>0.05).Compared with model group,levels of MAP,LVSP,HR and SOD were significantly increased in groups treated with RST(P<0.05),and showing concentration-dependence,while CK,Mb,CK-MB,ROS,MDA,IL-1β,iNOS levels,positive rate of IL-6,Caspase-3,Caspase-9 and p-JNK1/2 proteins expressions were significantly decreased(P<0.05),showing concentration-dependence,and there was no significant change in JNK1/2 protein expression(P>0.05).Conclusion:RST can regulate hemodynamics and immune response of rats with acute HF and inhibit oxidative stress by inhibiting JNK1/2 activation,showing concentration-dependence in a certain concentration range.更多还原