腺苷A1受体激动剂2-氯化腺苷抑制异丙肾上腺素诱导大鼠心肌肥厚的作用及机制

目的通过观察腺苷A1受体激动剂2-氯化腺苷(2-CADO)对异丙肾上腺素所致大鼠心肌肥厚的抑制作用及能量代谢的改变,探讨腺苷A1受体激动剂对肥厚心肌能量代谢的调节作用及其可能的作用机制。方法大剂量异丙肾上腺素皮下注射建立大鼠心肌肥厚模型。SD大鼠40只,雌雄不限,分为空白对照组、肥厚模型组、2-CADO组[2-氯化腺苷0.6 mg/(kg.d)腹腔注射]、普萘洛尔组[28 mg/(kg.d)普萘洛尔灌胃],每组10只。造模完毕第2天给药,连续8周。检测大鼠全心质量指数(HMI)、左心质量指数(LVMI);取左心室组织进行Masson染色,观察细胞横径(TDM)改变;碱水解法进行羟脯氨酸(Hyp)含量测定;紫外分光光度法检测心肌组织乳酸(LA)和游离脂肪酸(FFA)含量;激光共聚焦显微镜定量检测线粒体膜电位(MMP)。结果与空白对照组相比,肥厚模型组HMI、LVMI显著上升,心肌组织形态发生肥厚样改变;Hyp、LA和FFA含量显著升高,MMP下降了44%。与肥厚模型组相比,2-CADO组HMI、LVMI下降,TDM明显降低,Hyp、LA和FFA含量显著降低,MMP上升了50%。结论 2-CADO可以抑制异丙肾上腺素导致的心肌肥厚,其机制可能与改善肥厚心肌的能量代谢有关。

Effect and Mechanism of Adenosine A1 Receptor Agonist-2-Chlorinated Adenosine Inhibiting Isoproterenol-Induced Myocardial Hypertrophy in Rats

Aim To explore the roles of regulating energy metabolism and mechanism of adenosine A1 receptor agonist inhibiting myocardial hypertrophy by means of 2-chlorinated adenosine(2-CADO) on isoproterenol induced myocardial hypertrophy in rats.Methods High-dose isoproterenol subcutaneous injection to rats were used to establish myocardial hypertrophy model.Forty Sprague-Dawley rats were randomly divided into four groups with ten rats for each group: control group,isoproterenol induced myocardial hypertrophy group,isoproterenol induced myocardial hypertrophy+2-CADO(6 mg/(kg·d),intraperitoneal injection) group,isoproterenol induced myocardial hypertrophy+propranolol(28 mg/(kg·d),per os) group.Rats began to medicate at the second day after myocardial hypertrophy model establishment for 8 weeks.The whole heart quality index(HMI)and left heart quality index(LVMI) were detected.Left ventricular tissue was taken to observe the changes of TDM by Masson staining.Hydroxyproline(Hyp) content was determined by alkaline hydrolysis.Myocardial tissue lactate(LA) and free fatty acid(FFA) content were detected by UV spectrophotometry.Mitochondrial membrane potential(MMP) was detected by laser scanning confocal microscope.Results Compared with control group,in myocardial hypertrophy group HMI and LVMI were higher,the contents of Hyp,LA and FFA from left myocardial tissue were significantly increased and MMP decreased by 44%.Compared with myocardial hy-pertro phy group,in myocardial hypertrophy+2-CADO group and myocardial hypertrophy+propranolol group HMI,LVMI and the contents of Hyp,LA and FFA reduced,MMP increased by 50%.Conclusions Adenosine receptor agonist 2-CADO can inhibit myocardial hypertrophy induced by isoproterenol,the mechanism may be related to improving cardiac energy metabolism and preserving MMP.