瑞舒伐他汀抑制JNK1/2的活化对急性心力衰竭大鼠心脏血流动力学、氧化应激及免疫应答的调节

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...

Rosuvastatin in regulation of cardiac hemodynamics,oxidative stress and immune response in rats with acute heart failure by inhibiting JNK1/2 activation

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-1βwere 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.