别嘌醇与非布司他对家兔快速心房起搏房颤模型心房电重构的影响  

Effects of allopurinol and febuxostat on atrial electrical remodeling in a rabbit model of atrial fibrillation induced by rapid atrial pacing

作　　者：凡永艳 彭建军 王玉堂 李泱 Fan Yongyan;Peng Jianjun;Wang Yutang;Li Yang(Department of Cardiology,Beijing Shijitan Hospital of Capital Medical University,Beijing 100038,China;Department of Cardiology,First Medical Center,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]首都医科大学附属北京世纪坛医院心血管内科,北京100038 [2]中国人民解放军总医院第一医学中心心血管内科,北京100853

出　　处：《中华老年多器官疾病杂志》2024年第8期611-616,共6页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：国家自然科学基金(82370327);国家重点研发课题(2022YFA1104303-2)。

摘　　要：目的探讨黄嘌呤氧化酶(XO)抑制剂(别嘌醇与非布司他)对家兔快速心房起搏(RAP)房颤模型心房电重构的影响。方法24只健康雄性新西兰白兔,随机分为4组,假手术组(S组)、快速心房起搏组(P组)、快速心房起搏-别嘌醇干预组(ALL组)及快速心房起搏-非布司他干预组(FP组)。使用酶联免疫吸附测定(ELISA)法检测血清中超敏C反应蛋白(hs-CRP)、生长分化因子-15(GDF-15)、半乳糖凝集素-3的活性及左心房组织匀浆中超氧化物歧化酶(SOD)、XO、黄嘌呤脱氢酶(XDH)的活性。在起搏之前及4周的RAP之后分别进行电生理检查,测定基础起搏周长为200 ms时的心房有效不应期(AERP 200)和房颤诱发率。实时荧光定量聚合酶链式反应及蛋白质印记法检测钙离子电压门控通道亚基α1 C(Cav1.2)、钾离子电压门控通道亚族D3(Kv4.3)的信使RNA(mRNA)和蛋白表达。采用SPSS 26.0统计软件进行数据分析。根据数据类型分别采用单因素方差分析或χ^(2)检验进行组间比较。结果与S组相比,P组SOD活性明显降低,XO、XDH、hs-CRP、GDF-15及半乳糖凝集素-3水平显著升高,差异均有统计学意义(P<0.01)。应用XO抑制剂后,SOD活性回升明显,XO、hs-CRP、GDF-15及半乳糖凝集素-3活性均显著降低,差异均有统计学意义(P<0.05)。FP组SOD显著高于ALL组,XDH、hs-CRP、GDF-15及半乳糖凝集素-3活性显著低于ALL组,差异均有统计学意义(P<0.05);但FP组与ALL组XO水平比较,差异无统计学意义(P>0.05)。此外,FP组XDH水平明显低于P组,差异有统计学意义(P<0.01),但ALL组XDH水平与P组比较,差异无统计学意义(P>0.05)。RAP后P组的AERP 200明显低于S组(P<0.01),然而FP组的AERP 200显著高于P组和ALL组(P<0.05)。除S组外,P组、ALL组和FP组在RAP后的房颤诱发率均显著高于起搏之前基线状态下的房颤诱发率(P<0.05);应用XO抑制剂干预后,房颤诱发率有一定程度的降低,在FP组尤为明显。RAP可导致左心房�Objective The purpose of this study was to investigate the effects of xanthine oxidase(XO)inhibitors(allopurinol and febuxostat)on atrial electrical remodeling in a rabbit model of atrial fibrillation(AF)induced by rapid atrial pacing(RAP).Methods Twenty-four healthy male New Zealand white rabbits were randomly divided into four groups:sham-operated group(S group),RAP group(P group),RAP-allopurinol group(ALL group),and RAP-febuxostat group(FP group).Enzyme-linked immunosorbent assay(ELISA)kit was used to detect the activity of high-sensitivity C-reactive protein(hs-CRP),growth differentiation factor-15(GDF-15)and galectin-3,and the activity of superoxide dismutase(SOD)and the levels of XO and xanthine dehydrogenase(XDH)in left atrial tissues.Before pacing and four weeks after RAP,electrophysiological examinations were performed to evaluate the atrial effective refractory period at 200 ms(AERP 200)and the inducibility of AF.Real-time fluorescence quantitative polymerase chain reaction(PCR)and Western blotting were used to detect the messenger RNA(mRNA)and protein expressions of calcium voltage-gated channel subunitα1C(Cav1.2)and potassium voltage-gated channel subfamily D3(Kv4.3).SPSS statistics 26.0 was used for data analysis.According to different data type,one-way analysis of variance orχ^(2)test was used for data comparison between groups.Results Compared with S group,the SOD activity was significantly decreased,and the levels of XO,XDH,hs-CRP,GDF-15 and galectin-3 were increased in P group,and the differences were statistically significant(P<0.01).After using XO inhibitor,the activity of SOD recovered significantly,and the activities of XO,hs-CRP,GDF-15 and galectin-3 were significantly decreased,and the differences were statistically significant(P<0.05).The activity of SOD in FP group was significantly higher than in ALL group,whereas the activities of XDH,hs-CRP,GDF-15 and galectin-3 in FP group were obviously lower compared with ALL group(P<0.05).However,there was no significant difference in the level o

关 键 词：心房颤动 心房电重构 黄嘌呤氧化酶 非布司他 

分 类 号：R541.7[医药卫生—心血管疾病]