心房颤动心房肌β3-肾上腺素能受体通过NADPH氧化酶产生氧化应激研究  

Roles of β3 adrenergic receptor in oxidative stress of atrial fibrillation via NADPH oxidase pathway

作　　者：张苗苗[1] 李为民[1] 董晶妹 Zhang Miaomiao;Li Weimin;Dong Jingmei(Department of Cardiology,the First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院心血管内科

出　　处：《新医学》2019年第12期933-937,共5页Journal of New Medicine

摘　　要：目的研究心房颤动时β3-肾上腺素能受体(β3-AR)是否通过作用于尼克酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶产生氧化应激。方法建立快速心房起搏心房颤动兔模型,将40只成年家兔随机分为4组,分别为假手术组(Con组)、起搏7 d组(P7组)、β3-AR激动剂组(BRL组)和β3-AR抑制剂组(L组)。P7组、BRL组和L组在术后1周后分别给予β1-AR、β2-AR抑制剂纳多洛尔、纳多洛尔+β3-AR激动剂(BRL37344)和纳多洛尔+β3-AR抑制剂(L748337)。1周后取材,分别检测各组心房组织中超氧化物歧化酶(SOD)活力、丙二醛和NADPH氧化酶2(NOX2)含量。结果与Con组相比,P7组心房组织SOD活力降低(P<0.05),丙二醛、NOX2含量增加(P均<0.05)。给予β3-AR激动剂后,BRL组SOD活力进一步降低(P<0.05),NOX2含量增加(P<0.05)。给予β3-AR抑制剂后,L组SOD活力较P7组增加(P<0.05),丙二醛含量进一步降低(P<0.05),NOX2含量亦降低(P<0.05)。结论家兔快速心房起搏后心房肌发生氧化应激,激动β3-AR加重氧化应激,而抑制β3-AR后可减轻氧化应激。β3-AR可能通过NADPH氧化酶途径产生氧化应激。β3-AR和NADPH氧化酶有望成为防治心房颤动的新靶点。Objective To explore whether β3 adrenergic receptor contributed to the oxidative stress of atrial fibrillation by NADPH oxidases in the rabbit models with rapid atrial pacing.Methods The rabbit models with rapid atrial pacing were established.Forty rabbits were randomly divided into four groups:sham operation group(Con group),7-d pacing group(P7 group),β3 adrenergic receptor agonist group(BRL group)and β3 adrenergic receptor antagonist group(L group),respectively.Nadolol,Nadolol+BRL37344 and Nadolol+L748337 were administered at postoperative 1 week in the P7,BRL and L groups,respectively.At 1 week after sample collection,superoxide dismutase(SOD),malondialdehyde(MDA)and NADPH oxidase 2(NOX2)were quantitatively measured.Results Compared with the Con group,the SOD activity was significantly decrease,whereas MDA and NOX2 levels were remarkably increased in P7 group(all P<0.05).The SOD activity was significantly decreased,whereas the NOX2 level was considerably increased by β3 adrenergic receptor agonist(all P<0.05).After the administration of β3 adrenergic receptor agonist,the SOD activity was significantly higher,whereas the MDA and NOX2 levels in the Con group were considerably declined compared with those in the P7 group(all P<0.05).Conclusions Oxidative stress occurs in the atrial muscle of rabbit models with rapid atrial pacing.β3 adrenergic receptor agonist can aggravate oxidative stress,whereas inhibition of β3 adrenergic receptor agonist can alleviate the oxidative stress.β3 adrenergic receptor can induce oxidative stress via the NADPH oxidases signaling pathway.β3 adrenergic receptor and NADPH oxidases probably become novel therapeutic targets for atrial fibrillation.

关 键 词：心房颤动 氧化应激 Β3-肾上腺素能受体 尼克酰胺腺嘌呤二核苷酸磷酸氧化酶 

分 类 号：R54[医药卫生—心血管疾病]