N-乙酰半胱氨酸对心衰兔氧化应激和核因子NF-κB的干预研究  

Effect of N-acetylcysteine on oxidative stress and NF-κB in heart failure rabbits and its mechanism

作　　者：李燕[1] 万汝根 

机构地区：[1]南阳市中心医院心内二科,河南南阳473000 [2]东阳市人民医院心内科,浙江东阳322103

出　　处：《中国生化药物杂志》2015年第2期55-58,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：浙江省卫生厅(2011KYB151)

摘　　要：目的探讨N-乙酰半胱氨酸对心衰兔氧化应激和核因子NF-κB的干预研究。方法 40只健康成年大白兔,耳缘注射阿霉素制作心衰模型。8周后取造模成功的27只大白兔随机分为心衰组(n=14)和N-乙酰半胱氨酸组(NAC组,n=13),另取10只为对照组。对照组和心衰组给予注射生理盐水1 m L/(kg·d),NAC组给予注射NAC 300 mg/(kg·d)。干预4周后,测定各组兔超声心动图参数(LVEDD、LVESD、IVST、EF、FS)、血清及心肌组织总抗氧化能力;酶联免疫检测各组兔血清和心肌组织8-iso-PGF2α的含量;免疫组化和Western blot检测NF-κB p65及其抑制物IκB-α在左室心肌细胞的表达和核结合活性的改变。结果与对照组相比,心衰组兔左室舒张期末内径(LVEDD)、左室收缩期末内径(LVESD)明显增大(P<0.05);射血分数(EF)与短轴缩短率(FS)明显降低(P<0.05),室间隔厚度(IVST)未见明显变薄。心衰组血清和心肌的总抗氧化能力均低于对照组(P<0.01);与心衰组比较,NAC干预组总抗氧化能力明显升高(P<0.05),与对照组比较差异无统计学意义。NAC注射组较心衰组心肌细胞NF-κB p65向核内移位表达的阳性细胞明显减少,NAC治疗后兔心肌细胞NF-κB p65的表达较心衰组减少(P<0.05),IκB-α表达较心衰组多(P<0.05)。心衰后给予NAC干预的兔血清和心肌组织8-iso-PGF2α含量较心衰组显著降低(P<0.05),血清和心肌8-iso-PGF2α的含量均与心功能显著相关(r=0.975,P<0.005;r=0.974,P<0.05)。结论氧化应激参与了心力衰竭的发生和心功能的恶化;NAC可通过抑制氧化应激,拮抗NF-κB的活化和其在核内的表达,减少心肌细胞凋亡及炎症反应,有效改善心功能,保护心肌。Objective To explore the intervention of N-acetylcysteine on oxidative stress and NF-κB in heart failure rabbit and its mechanism.Methods 40 healthy mature rabbits with heart failure caused by adriamycin administration through ear venous were modeled. 27 rabbits were survival after modeling 8 weeks,and randomly divided into heart failure group（ n = 14） and N-acetylcysteine group（ NAC,n = 13）. 10 another healthy rabbits were chosen as control group. The heart failure group and control group were administrated with saline 1 m L /（ kg·d） and NAC group with NAC 300 mg /（ kg·d）. After four weeks,echocardiography parameters（ LVEDD,LVESD,IVST,EF and FS）,total antioxidant capacity in serum and cardiac muscle tissue of each group were measured. The content of 8-iso-PGF2αin serum and myocardial tissue were detected by ELISA. The change of NF-κB p65 and its inhibitor IκB-α protein expression and nuclear binding activity in the left ventricular myocardial cell were detected by immunohistochemical method and Western blot. Results Compared with control group,the left ventricular end diastolic diameter and left ventricular end systolic diameter in heart failure group increased（ P〈0. 05）,the ejection fraction and fractional shortening decreased（ P〈0. 05）,but interventricular septal thickness was not showing significantly thinner. Total antioxidant capacity in serum and myocardium of heart failure group were lower than those of control group（ P〈0. 01）,Compared with heart failure group,the total antioxidant capacity increased in NAC group（ P〈0. 05）,and the total antioxidant capacity in control group and NAC group had no statistical difference. The numbers of positive myocardial cells of NF-κB p65 nuclear translocation in NAC group significantly reduced than those in heart failure group NF-κB p65 expression in myocardium of NAC group was lower than heart failure group（ P〈0. 05）,and IκB-αexpression was higher than heart failure group（ P〈0. 05）. The content of 8-iso-P

关 键 词：心力衰竭 NF—κB 细胞凋亡 氧化应激 N-乙酰半胱氨酸 

分 类 号：R96[医药卫生—药理学]