芍药苷对小鼠急性心肌梗死后心室重构的影响

Effects of paeoniflorin on ventricular remodeling in mouse with acute myocardial infarction

目的研究芍药苷对小鼠急性心肌梗死(AMI)心室重构的作用及其相关机制。方法实验采用手术构建AMI小鼠模型,根据饮食不同分为对照组,模型组,低剂量芍药苷组,高剂量芍药苷组。记录2周内心脏破裂发生率,超声探查心脏改变,逆转录(Real-time)PCR分析心室中炎症基因白细胞介素-6、转化生长因子-α、血管细胞黏附因子-1、核因子-κB(IL-6、TFN-α、VCAM-1、NF-κB)、重构相关基因(MMP-2,9,TIMP-2)的表达。结果模型组心脏破裂率为43.8%,而低高两个剂量组心脏破裂率均为12.5%。心脏超声提示芍药苷干预后心脏扩大程度减弱、心室壁稍变薄、收缩力增强,整体心室重构程度较轻(P<0.05),但不同剂量组间未见差异性(P>0.05)。Real-Time PCR结果显示,模型组小鼠心室炎症基因及重构相关基因基质金属蛋白(MMP-2,MMP-9)表达均显著上调(P<0.05),且TIMP-2表达降低,芍药苷干预后明显逆转(P<0.05),且与剂量有关。结论芍药苷能够降低心脏破裂率,改善心室结构,减轻心脏重构,这一作用可能与调控NF-κB减少局部炎症及抑制基质金属蛋白酶活力有密切关系。

[Objective] To investigate the effects of paeoniflorin on ventricular remodeling in mouse with acute myocardial infarction（AMI）,analyze its mechanism.[Methods]The mouse model AMI was made by operation,and the animals were divided into four groups according to the different diet： control group,model group,low dose paeoniflorin group,and high dose paeoniflorin group. The incidence of cardiac rupture in 2 weeks was recorded after operation,and the changes of heart shape were measured by ultrasound. The expressions of inflammation genes（IL-6,TFN-α,VCAM-1 and NF-κB） and remodeling gene（MMP-2,9,TIMP-2）were detected by real-time PCR.[Results]The incidence of cardiac rupture in model group was 43.8%,while that in two paeoniflorin groups were both 12.5%. The ultrasound test indicated that enlarged ventricle,the weak ventricular wall,and the poor myocardial contractility were attenuated by paeoniflorin treatment,that is the whole ventricular remodeling was lessened（P〈0.05）,but no significant difference was found between different dose groups（P〈0.05）. Real-Time PCR suggested that the expressions of inflammatory gene and remodeling gene 9（MMP-2 and MMP-9） in model group were significantly increased（P〈0.05）,the level of TIMP-2 m RNA reduced. However,these changes were attenuated after paeoniflorin treatment（P〈0.05）,and there was a dosedependent effect. [Conclusion] Paeoniflorin can reduce the incidence of cardiac rupture,improve the cardiac structure and relieve the cardiac remodeling,which may be related to the regulation of NF-κB,reduction of the local inflammation and inhibition of matrix metalloproteinase activity.