中文摘要：

目的：分别应用选择性β3肾上腺素受体（β3-adrenoceptor,β3-AR）阻断剂及激动剂对异丙肾上腺素（isoproterenol,ISO）致慢性心力衰竭（chronic heart failure,CHF）模型大鼠进行干预,观察β3-AR是否在CHF进展中介导心肌纤维化。方法：90只健康雄性Wistar大鼠随机分为4组：1正常对照组：腹腔注射0.9%氯化钠;2 CHF组：腹腔注射ISO＋0.9%氯化钠;3β3-AR激动剂干预心衰组（BRL组）：腹腔注射ISO＋尾静脉注射BRL37344;4β3-AR抑制剂干预心衰组（SR组）：腹腔注射ISO＋SR59230A。干预结束后检测血流动力学指标,心肌病理学变化,胶原容积分数（CVF）,心肌羟脯氨酸（Hyp）含量等。结果：1模型组大鼠在12周后心功能明显下降,出现心肌重构,CHF模型成功建立。2BRL组大鼠较CHF组LVSP、±dp/dtmax降低,LVEDP、LVW/BW升高（P〈0.05或P〈0.01）,心肌出现明显变性及纤维化改变,CVF升高（P〈0.05）,心肌Hyp含量升高（P〈0.05）;SR组较CHF组HR、LVEDP下降（P〈0.05或P〈0.01）,LVSP显著升高（P〈0.05）。结论：1腹腔注射ISO可成功复制CHF大鼠模型。2β3-AR激动后可促进心肌纤维化,提示β3-AR可能通过介导心肌重构参与CHF进展。

英文摘要：

Objective：To observe the effects ofβ3-adrenoceptor on myocardial fibrosis in heart failure by usingβ3-adrenoceptor agonist and inhibitor on isoproterenol-induced rat model of heart failure.Method：Ninety healthy male Wistar rats were divided into four groups randomly ：1Normal control group：received intraperitoneal injection of saline;2Heart failure control group：received intraperitoneal injection of isoproterenol（ISO）＋saline;3BRL group：received intraperitoneal injection of ISO＋Intravenous injection ofβ3-adrenoceptor agonist BRL37344;4SR group：received intraperitoneal injection of ISO＋β3-adrenoceptor inhibitor SR59230 A.Then hemodynamics,myocardial pathological changes,collagen volume fraction,myocardial hydroxyproline content were calculated for analysis.Result：1The heart failure model was successfully established as evidenced by multifocal degeneration of myocyte,deposition of collagen and impaired cardiac function after 12 weeks of intraperitoneal injection of ISO.2In BRL group,compared with the CHF group,LVSP,±dp/dtmax were significantly lower and LVEDP,LVW/BW were significantly higher（P0.05 or P0.01）,and there was a significant change of myocardial degeneration and fibrosis,as well as a increased level of CVF and a increased content of myocardial hydroxyproline（P0.05）.In SR group,HR、LVEDP were significantly lower,LVSP was increased（P0.05）,when compared with the CHF group.Conclusion：1Rats heart failure model can be successfully induced by intraperitoneal injection of isoproterenol.2After excited,β3-AR can aggravate myocardial fibrosis,suggesting thatβ3-AR may participate in the progression of heart failure by mediated myocardial remodeling.