脑钠肽对压力负荷诱导的小鼠心力衰竭的影响及作用机制  

Effect of Treatment with BNP on Mice of Heart Failure Induced by Pressure Overload In Vivo

作　　者：刘帅烨 周越 何昕[1] 黄艺仪[3] 陈艺莉[1] 何建桂[1] LIU Shuai-ye;ZHOU Yue;HE Kin;HUANG Yi-yi;CHEN Yi-li;HE Jian-gui(Department of Cardiology;Department of Critical Care Medicine,The First Affiliated Hospital of Sun Yat-Sen University;Key Laboratory on Assisted Circulation,Ministry of Health,Guangzhou 510080,China;State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,Nation Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medieal College,Beijing 100037,China)

机构地区：[1]中山大学附属第一医院心内科//卫生部辅助循环重点实验室 [2]北京协和医学院//中国医学科学院国家心血管病中心阜外医院,北京100000 [3]中山大学附属第一医院重症医学科,广东广州510080

出　　处：《中山大学学报（医学版）》2018年第4期510-520,共11页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(2014A030313019;2017A030313795);广州市科技计划项目(201707010124)

摘　　要：【目的】探讨脑钠肽(BNP)对压力负荷诱导的小鼠心力衰竭的影响和作用机制。【方法】用编码人源性脑钠肽(hBNP)基因的腺相关病毒(AAV9)转染C57/B6J小鼠促进其体内表达hBNP,3周后行主动脉缩窄术构建压力负荷诱导的小鼠心力衰竭模型。构建模型4周后通过超声心动图、心脏及肺脏质量比值来检测心脏功能及结构变化,并使用Q-PCR技术来检测心肌肥厚标志物(ANP)mRNA水平。通过免疫荧光技术观察心肌组织内毛细血管的变化,Image-J软件测量毛细血管密度和毛细血管/心肌细胞比值,Q-PCR和Western-Blotting检测心肌组织内血管新生因子(AngⅠ,VEGFA)mRNA转录和蛋白表达水平。【结果】AAV9-hBNP能促进小鼠体内hBNP的表达。hBNP不仅显著改善压力负荷诱导的心力衰竭(P<0.05),且能降低心脏、肺脏质量比值以及肥厚标志物mRNA转录水平(P<0.05)。hBNP增加小鼠心力衰竭模型心肌组织内毛细血管以及血管新生因子mRNA转录和蛋白表达水平(P<0.05)。【结论】BNP可能通过促进血管新生因子的表达来调控血管新生从而改善压力负荷诱导的心力衰竭。【Objective】The purpose of this study was to investigate the effect of brain natriuretic peptide（BNP）onmice of heart failure induced by pressure overload in vivo and to clarify the mechanism underlying this effect.【Methods】C57/B6 J mice were transfected with adeno-associated virus（serotype 9,AAV9）encoding the human BNP（hBNP）gene,and the mice of heart failure induced by pressure overload were generated by 3 weeks of aortic banding. After 4 weeks of aortic banding,echocardiography,the ratios of heart weight/body weight（HW/BW）and lung weight/bodyweight（LW/BW）were used to evaluate the changes of cardiac function and structure,and the mRNA expression level ofcardiac hypertrophic marker（ANP） was detected by Q-PCR. The changes of cardiac capillaries were observed byimmunofluorescence staining,and the ratio of capillary/myocyte and capillaries density were determined by Image-Jsoftware. The mRNA and protein expression of cardiac angiogenesis factors（VEGFA,AngⅠ）were examined by Q-PCRand Western blotting.【Result】Our data showed that AVV9-hBNP notably promoted overexpression of hBNP in mice.Treatment with hBNP not only significantly improved heart failure induced by pressure overload（P 〈0.05）,but alsodecreased the ratios of HW/BW and LW/BW as well as the mRNA expression level of hypertrophic marker（P〈 0.05）.Furthermore,Treatment with hBNP increased cardiac angiogenesis and the mRNA and protein expression level ofangiogenesis factors in mice of heart failure（P 〈0.05）. 【Conclusion】 Treatment withBNP can improve pressureoverload-induced heart failure by regulating angiogenesis through promoting the expression of angiogenesis factors.

关 键 词：脑钠肽 心力衰竭 血管新生 压力负荷 小鼠 

分 类 号：Q956[生物学—动物学]