丹皮酚对急性心肌梗死后心室重构模型大鼠RAS的影响

Effects of paeonol on RAS occurred on the development of ventricular remodeling after acute myocardial infarction in rats

目的观察丹皮酚对急性心肌梗死(AMI)后心室重构模型大鼠肾素-血管紧张素系统(RAS)的影响。方法对健康雄性SD大鼠进行左冠状动脉前降支结扎,复制AMI模型。设假手术组、模型组、卡托普利组、丹皮酚低剂量(6 mg/kg)组、丹皮酚中剂量(9 mg/kg)组和丹皮酚高剂量(12 mg/kg)组。造模成功并存活下来的大鼠,分别给予各组不同药物处理。用药4周后取材,采用HE染色法观察心肌组织病理变化;采用实时荧光定量PCR(Real-TimePCR)检测各组心肌组织中血管紧张素原(AGT)、血管紧张素Ⅱ受体(AGTR)1和内皮缩血管肽1(ET)-1 m RNA水平表达情况并进行分析;采用蛋白质免疫印迹法(Western blot)检测各组大鼠心肌组织中肽基二肽酶A(ACE),血管紧张素Ⅱ(Ang)-Ⅱ和AGTR1的蛋白表达水平。结果与假手术组比较,模型组大鼠心肌组织中AGT、AGTR1、ET-1的m RNA表达明显升高,Ang-Ⅱ、ACE、AGTR1的蛋白表达亦显著升高(P<0.05);与模型组比较,其在丹皮酚高剂量组和卡托普利组心肌组织中m RNA表达以及蛋白表达均显著降低(P<0.05)。丹皮酚对降低其m RNA表达和蛋白表达存在明显的剂量依赖性。结论丹皮酚能够延缓大鼠AMI后心室重构,其机制可能与抑制RAS的过度激活有关。

Objective To investigate the effects of paeonol on renin-angiotensin system（RAS） occurred on the devel-opment of ventricular remodeling after acute myocardial infarction（AMI） in rats.Methods The left anterior descending cor-onary artery was ligated to establish the model of AMI in male SD rats.Six groups were set up：sham-operation group,AMImodel group,captopril control group,paeonol low dose group（6 mg/kg）,paeonol middle dose group（9 mg/kg） and paeonolhigh dose group（12 mg/kg）.Rats were given treatment for 4 weeks after the AMI model was established.HE staining wasused to observe changes of myocardial tissue.Real-time PCR was used to detect the m RNA levels of angiotensinogen（AGT）,angiotensinⅡ receptor type1（AGTR1） and endothelin（ET）-1 of six groups.Western blot assay was used to detect the proteinlevels of peptidyl-dipeptidase A（ACE）,angiotensin Ⅱ（Ang）-Ⅱand AGTR1 in six groups.Results The transcription ofAGT,AGTR1,ET-1m RNA and the expressions of ACE,Ang-Ⅱand AGTR1 protein were significantly higher in myocardialtissue of AMI rats than those of sham-operation rats（P〈0.05）.Compared with model group,the expressions of AGT,AG-TR1,ET-1m RNA and ACE,Ang-Ⅱ,AGTR1 protein were significantly decreased in paeonol high dose group and captoprilcontrol group（P〈0.05）.Paeonol reduced the expressions of those m RNA and protein levels in a significant dose dependentmanner.Conclusion Paeonol can slow down the deterioration of the ventricular remodeling after AMI in rats,which maybe related to the inhibition of over-activation of RAS.