摘要
目的:观察新化合物N-{4-[4-(5-苯基-1H-四唑-1-基)丁氧基]苯基}乙酰胺(HYY-002)抗房颤作用。方法:雄性SD大鼠,随机分为正常组、模型组、胺碘酮,低剂量(2 mg/kg)和高剂量HYY-002(10 mg/kg)组。大鼠尾静脉注射乙酰胆碱合并氯化钙[CaCl2(10 mg/kg)-Ach(66μg/kg)]10 d制备房颤模型。治疗组从造模第4天开始,每天造模前1 h,分别腹腔注射胺碘酮(30 mg/kg)或灌胃给予低、高剂量HYY-002。Ⅱ导联心电图记录房颤持续时间,测定各组大鼠心房有效不应期(AERP),血浆炎性因子及microRNA-135a(miR-135a)的变化。结果:模型组大鼠房颤时间持续延长,AERP较正常组缩短[(61.83±4.13)vs.(72.70±7.05)ms,P<0.05],血浆中炎性因子TNF-α、IL-1和IL-6的含量高于正常组。HYY-002给药剂量10 mg/kg能有效缩短房颤持续时间[(6.42±1.38)vs.(16.32±1.31)s,P<0.01],缓解房颤引起的AERP缩短[(77.78±3.79)vs.(61.83±4.13)ms,P<0.01],降低血浆中炎性因子浓度,效果与胺碘酮相当。与正常组相比,模型组血浆miR-135a表达明显降低(P<0.01),HYY-002给药后miR-135a在血浆中含量显著上升(P<0.01)。结论:HYY-002对房颤有显著治疗效果,miR-135a可能参与房颤发生发展过程。
AIM:To investigate the inhibitory effect of HYY-002 on atrial fibrillation(AF).METHODS:Male SD rats were randomized into 5 groups:normal,model,amiodarone(30 mg/kg,i.p.),low-dose and high-dose HYY-002 group.The rats were administrated Ach-CaCl2(i.v.)for 10 days to establish rat AF model.From the 4th day,rats in treatment group were treated with amiodarone(30 mg/kg,i.p.)and HYY-002(2 mg/kg,10 mg/kg,i.g.)1 hour before modeling.AF duration and ECG parameters were measured every day.On the 11th day,AERP of every rat were measured and the inflammatory cytokines and miR-135a in plasma were detected.RESULTS:In the model group,AF duration increased persistently and AERP shortened distinctly compared with normal group[(61.83±4.13)vs.(72.70±7.05)ms,P<0.05].The expression of TNF-α,IL-1 and IL-6 in plasma of model group were higher than normal group(P<0.05).High dose of HYY-002(10 mg/kg)shortened AF duration effectively[(6.42±1.38)vs.(16.32±1.31)s,P<0.01 vs.model group],relieved the shortening of AERP induced by AF[(77.78±3.79)vs.(61.83±4.13)ms,P<0.01 vs.model group]and lowered the inflammatory cytokines level in plasma.Compared with normal group,the expression of miR-135a in plasma of model group was down-regulated obviously(P<0.01).CONCLUSION:HYY-002 has a significant therapeutic effect on AF,and miR-135a might be involved in the development of AF.
作者
杨蕾熙
冯凯
凡学婷
尉延春
刘婷婷
汤依群
YANG Leixi;FENG Kai;FAN Xueting;WEI Yanchun;LIU Tingting;TANG Yiqun(Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu, China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2019年第12期1347-1352,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家新药创制重大专项(2011ZX09401-021)
