心肌细胞特异性过表达内脂素对血管紧张素Ⅱ诱导的小鼠心肌肥大的影响

Effect of cardiomyocyte-specific overexpression of visfatin on cardiac hypertrophy induced by angiotensinⅡin mice

目的观察内脂素对血管紧张素Ⅱ(AngⅡ)诱导的小鼠心肌肥大的影响,探讨内脂素在心肌肥大中的作用及可能机制。方法取雄性C57BL/6及心肌细胞特异性内脂素转基因小鼠各8只,使用微型渗透释放泵以1.3 mg/(kg·d)的速度持续泵入AngⅡ制备心肌肥大模型(野生AngⅡ组和转基因AngⅡ组)。另各取8只C57BL/6及心肌细胞特异性内脂素转基因小鼠以相同速度持续泵入等体积的生理盐水作为对照(野生对照组和转基因对照组)。4周后称取小鼠心脏重量及体质量,计算各组小鼠心脏质量指数(HMI),行苏木精-伊红染色观察心肌细胞横截面积,应用实时定量聚合酶链式反应(RT-qPCR)技术检测脑利尿钠肽(BNP)和β-肌球蛋白重链(β-MHC)的mRNA表达水平,Western blot测量Toll样受体4(TLR4)及髓样分化因子88(MyD88)蛋白表达。结果野生AngⅡ组的HMI较野生对照组增加[(5.11±0.23)比(4.16±0.15)mg/g,t=95.75,P<0.05],心肌细胞横截面积增大,BNP、β-MHC的mRNA表达水平增高。与野生AngⅡ组相比,转基因AngⅡ组HMI进一步升高[(5.51±0.18)比(5.11±0.23)mg/g,t=15.01,P<0.05],心肌细胞横截面积增大,BNP、β-MHC的mRNA表达水平增高,TLR4/MyD88蛋白含量增多。结论内脂素可促进AngⅡ诱导的心肌肥大,其机制可能与上调TLR4/MyD88表达有关。

Objective To observe the effect of visfatin on angiotensinⅡ(AngⅡ)-induced myocardial hypertrophy,and investigate the role and potential mechanism of visfantin on myocardial hypertroghy.Methods Eight male C57BL/6 and cardiomyocyte-specific visfatin transgenic mice were respectively pumped with AngⅡat a rate of 1.3 mg/(kg·d)continuously to prepare the myocardial hypertrophy models(AngⅡWT group and AngⅡTg group).In addition,eight C57BL/6 and cardiomyocyte-specific visfatin transgenic mice were respectively continuously pumped with equal volume of normal saline at the same speed as the control(Saline WT group and Saline Tg group).After 4 weeks,the heart and body weight of mice were measured to calculate the heart mass index(HMI),the cross-sectional area of myocardial cells were measured by hematoxylin-eosin staining,the mRNA expression of B-type natriuretic peptide(BNP)andβ-myosin heavy chain(β-MHC)were detected by real-time quantitative polymerase chain reaction(RT-qPCR),and Toll-like receptor 4(TLR4)and myeloid differentiation primary response 88(MyD88)were measured by Western blot.Results Compared with the Saline WT group,the HMI of the AngⅡWT group was elevated[(5.11±0.23)vs(4.16±0.15)mg/g,t=95.75,P0.05],the cross-sectional area of cardiomyocytes was increased,and the mRNA expression of BNP andβ-MHC were enhanced.Compared with the AngⅡWT group,the AngⅡTg group had higher HMI[(5.51±0.18)vs(5.11±0.23)mg/g,t=15.01,P0.05],larger cardiomyocyte cross-sectional area,higher mRNA expression of BNP andβ-MHC,and higher TLR/MyD88 protein content.Conclusion Visfatin promotes cardiac hypertrophy induced by angiotensinⅡ,and the mechanism may be related to the upregulation of TLR4/MyD88 signaling pathway.