异丙肾上腺素下调NADPH氧化酶负调控瘦素表达加剧db/db小鼠心功能异常  

Isoproterenol Exacerbates Cardiac Dysfunction in db/db Mice by Decreasing Leptin Expression Which is Mediated by NADPH Oxidase Negatively

作　　者：陈鹏 王萍[1] CHEN Peng;WANG Ping(Department of Cardiology,Xiangyang City Central Hospital,Xiangyang 441000,China)

机构地区：[1]湖北省襄阳市中心医院心内科,襄阳441000

出　　处：《微循环学杂志》2019年第1期13-17,27,共6页Chinese Journal of Microcirculation

摘　　要：目的:分析异丙肾上腺素加剧db/db小鼠心功能损伤的瘦素参与机制及NADPH氧化酶的调控作用。方法:18只野生型小鼠和18只db/db小鼠分别随机分为3组:对照组、异丙肾上腺素组和NADPH氧化酶apocynin组(n均=6)。除对照组外,其余两组小鼠给予异丙肾上腺素皮下注射(1mg/kg),连续6天,apocynin组小鼠第4天起给予apocynin(100mg/kg)灌胃治疗。分析各组小鼠心脏指数,并检测心肌组织中NADPH氧化酶亚基、瘦素及基质金属蛋白酶(MMP)和抑制剂表达。结果:与对照组比较,异丙肾上腺素组小鼠心功能明显异常(P<0.01),且NADPH氧化酶亚基p22phox、p47phox、p67phox、gp91phox及瘦素表达明显升高(P<0.01),MMP2/9和TIMP1/2也明显升高(P<0.01),而apocynin组小鼠上述指标异常得到明显改善(P<0.01)。结论:异丙肾上腺素通过下调NADPH氧化酶负调控瘦素表达加剧db/db小鼠心肌功能异常。Objective:To explore the involvement of leptin in the pathogenesis of cardiac dysfunction exacerbated by isoproterenol in db/db mice.Method:db/db and wild type mice were divided into 3 groups randomly:control,isoproterenol(1mg/kg,s.c.,6d)and NADNH oxidase inhibitor apocynin(100mg/kg,p.o.from the 4th day)group.At the same time,cardiomyocytes isolated from db/db or wild type mice were mediated with isoproterenol for 24h and received apocynin treatment during the last 12h.The expression of NADPH oxidase,leptin,MMPs/TIMPs were detected by Western Blotting and(or)immunocytochemistry.Results:In db/db mice,severe cardiac dysfunction were found in isoproterenol group when compared with wild type mice(P<0.01).The results also revealed that p22phox,p47phox,p67phox,gp91phox as well as leptin were increased dramatically in isoproterenol treated db/db mice(P<0.01),associated with MMP2/9 and TIMP1/2 when compared with wild type(P<0.01).Conclusion:Isoproterenol exacerbating cardiac dysfunction in db/db mice is related with decreased leptin expression which is cediated by NADPH oxidase negatively.

关 键 词：心功能 瘦素 NADPH氧化酶 DB/DB小鼠 异丙肾上腺素 

分 类 号：R542.2[医药卫生—心血管疾病]