基于AngII-NOx-ROS信号通路探索黄杨宁对心房颤动犬氧化应激的影响  

Effect of Huangyangning on oxidative stress in dogs with atrial fibrillation via the AngII-NOx-ROS signaling pathway

作　　者：冯光玲 毛文锋 郅强 王贺[3] 解金红[3] FENG Guangling;MAO Wenfeng;ZHI Qiang;WANG He;XIE Jinhong(Guiyang First People’s Hospital,Guiyang 550000,China;the First Clinical College of Henan University of Traditional Chinese Medicine,Zhengzhou 450000;The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000)

机构地区：[1]贵阳市第一人民医院,贵阳550000 [2]河南中医药大学第一临床医学院,郑州450000 [3]河南中医药大学第一附属医院,郑州450000

出　　处：《中国比较医学杂志》2023年第3期17-23,共7页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金委员会面上项目(81473508);河南省自然科学基金项目(212300410370)。

摘　　要：目的观察黄杨宁对心房颤动犬体内氧化应激水平的影响。方法15只比格犬随机分为5组:空白对照组、模型组、假手术组、黄杨宁组(0.24 mg/kg)、普罗布考组(7.58 mg/kg)。造模经股静脉穿刺置入双极电极于犬右心耳,尾端连接高频起搏器,给予高频刺激构建犬房颤模型。模型成功标准:起搏1周后,心电图证实有房颤发生或程控过程中诱发房颤发作,则认为模型成功。术后1 d开始灌胃,术后1周开始心房起搏,4周后取材。马松染色观察心肌纤维变化;ELISA检测血管紧张素Ⅱ(AngII)、还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)血清含量;化学发光法检测活性氧(ROS)的含量、比色法测定总抗氧化能力(TAC);RT-PCR、Western blot测定NADPH氧化酶(Nox)亚单位基因p22、p47表达水平。结果与空白组对比,模型组的血清AngII、NADPH明显上升(P<0.05)、ROS/TAC水平明显升高(P<0.05);p22、p47基因表达明显升高;p22、p47蛋白表达升高。黄杨宁及普罗布考干预后,血清NADPH水平无明显升高;ROS/TAC水平均低于模型组,有显著性差异(P<0.05);Rac-1、p22、p47基因表达低于模型组,统计学有显著性意义(P<0.05);P22、P47蛋白表达均低于模型组,有显著的统计学意义(P<0.05)。结论黄杨宁可减轻房颤犬的氧化应激水平,其作用机制可能与AngII-NOx-ROS信号通路有关。ObjectiveTo observe the effect of Huangyangning on oxidative stress in dogs with atrial fibrillation.MethodsFifteen beagle dogs were randomly divided into five groups:blank control,model,sham-operated,Huangyangning(0.24 mg/kg),and probenecid(7.58 mg/kg)groups.A canine atrial fibrillation model was established by placing bipolar electrodes in the right heart ear through femoral vein puncture and connecting a high frequency pacemaker at the caudal end to provide high frequency stimulation.Model establishment was considered successful when atrial fibrillation was confirmed by an electrocardiogram after 1 week of pacing or when an episode of atrial fibrillation was induced during the programmed control.Gavage was started at 1 day after surgery,atrial pacing was started at 1 week after surgery,and samples were collected after 4 weeks.Myocardial fiber changes were observed by Masson staining.Serum levels of angiotensinII(AngII)and reduced nicotinamide adenine dinucleotide phosphate(NADPH)were measured by ELISA.Reactive oxygen species(ROS)and total antioxidant capacity(TAC)were measured by chemiluminescence.Expression of NADPH oxidase(Nox)subunit genes p22 and p47 was measured by RT-PCR and Western blot.Results Compared with the blank group,serum AngII and NADPH were significantly increased(P<0.05)and ROS/TAC levels were significantly increased(P<0.05)in the model group,expression of p22 and p47 genes was significantly increased,and expression of p22 and p47 proteins was increased.There was no significant increase in the serum NADPH level after treatment with Huangyangning or probenecid.ROS/TAC levels were significantly lower than in the model group(P<0.05).Rac-1,p22 and p47 gene expression was significantly lower than in the model group(P<0.05).p22 and p47 protein expression was also significantly lower than in the model group(P<0.05).ConclusionsHuangyangning reduces oxidative stress in dogs with atrial fibrillation,and its mechanism of action may be related to the AngII-NOx-ROS signaling pathway.

关 键 词：心房颤动 犬 黄杨宁 氧化应激 

分 类 号：R-33[医药卫生]