N-乙酰半胱氨酸对大鼠压力负荷性心力衰竭保护作用研究

Protective effect of N-acetylcysteine on rats with pressure overload heart failure

目的探讨N-乙酰半胱氨酸(NAC)对大鼠压力负荷性心力衰竭的保护作用。方法将30只普通级8周龄雄性SD大鼠分入对照组、模型组和NAC给药组。所有大鼠术后干预3周,饲养至第7周后,测量每组剩余大鼠心脏质量,并计算心脏质量指数(HWI),通过实时聚合酶链反应和Western blot技术检测黑色素瘤分化相关基因5(MDA5)、肌醇依赖酶1α(IRE1α)、超氧化物歧化酶-1(SOD-1)和氧化应激Nrf2/Keap1通路关键基因及蛋白表达。结果与对照组比较,模型组大鼠心脏质量、HWI显著增加,氧化应激指标MDA5与IRE1αmRNA及蛋白表达均明显升高,SOD-1 mRNA及蛋白表达显著降低,氧化应激通路Nrf2与Keap1 mRNA及蛋白表达均显著降低,差异均有统计学意义(P<0.05)。与模型组比较,给药组大鼠心脏质量、HWI显著降低,MDA5与IRE1αmRNA及蛋白水平明显降低,而SOD-1 mRNA及蛋白水平明显升高,Nrf2与Keap1 mRNA及蛋白平均明显上调,差异均有统计学意义(P<0.05)。结论 NAC对大鼠压力负荷性心力衰竭有保护作用,其作用机制可能通过调控氧化应激Nrf2/Keap1通路有关。

Objective To investigate the protective effect of N-acetylcysteine(NAC)on stress overload heart failure in rats.Methods Thirty 8-week-old male SD rats were divided into the control group,model group,NAC administration group.After 3 weeks of intervention and 7 weeks of feeding,the heart weight of the remaining rats in each group was measured and the heart weight index(HWI)was calculated.The genes of melanoma differentiation-related gene 5(MDA5),inositol-dependent enzyme 1α(IRE1α),superoxide dismutase-1(SOD-1)and oxidative stress Nrf2/Keap1 pathway were detected by real-time polymerase chain reaction(PCR)and Western blot.Results Compared with the control group,the heart weight and HWI of the model group were significantly increased,the mRNA and protein levels of MDA5 and IRE1αwere significantly increased,the mRNA and protein levels of SOD-1 were significantly reduced,mRNA and protein levels of Nrf2 and Keap1 in the oxidative stress pathway were significantly reduced,and the differences were statistically significant(P<0.05).Compared with the model group,the heart weight and HWI of rats in the administration group were significantly reduced,while the mRNA and protein levels of MDA5 and IRE1 were significantly reduced,while the mRNA and protein levels of SOD-1 were significantly increased,and the mRNA and protein levels of Nrf2 and Keap1 were significantly up-regulated on average(P<0.05).Conclusion NAC has protective effect on pressure-overload heart failure in rats,and its mechanism may be related to the regulation of oxidative stress Nrf2/Keap1 pathway.