丹皮酚对急性心肌梗死大鼠Smad2,Smad3,Smad7 mRNA含量表达的影响

Effect of Paeonol on Smad2,Smad3,Smad7 mRNA Expression in Acute Myocardial Infarction Rat Heart

目的:研究丹皮酚对急性心肌梗死(AMI)大鼠进行性心室重构的保护作用及其对转化生长因子-β(TGF-β)/Smads信号通路上Smad2,Smad3,Smad7 mRNA含量表达的影响。并探讨其延缓甚至逆转心室重构的分子机制。方法:采用左冠状前降支(LAD)结扎法制作在体大鼠急性心肌梗死模型,在心电图评价的基础上,将造模成功的大鼠随机分为模型组、丹皮酚低、中、高剂量组、卡托普利组,另有只穿线不结扎的假手术组,每组10只,共6组。丹皮酚低、中、高剂量组分别给予ip8,12,16 mg·kg-1剂量的丹皮酚注射液,假手术组与模型组每天ip等体积生理盐水,卡托普利组用蒸馏水稀释其片剂碾成的药粉,给予ig 10 mg·kg-1,所有干预均1次/d;4周后分别取材,测定各组大鼠心脏质量指数及梗死面积,采用实时荧光定量RTq PCR技术检测各组心肌组织Smad2,Smad3,Smad7 mRNA的表达水平。结果:与模型组比较,丹皮酚低、中、高剂量组、卡托普利组大鼠心肌梗死面积明显减少(P<0.05),心脏质量指数降低(P<0.05);模型组Smad2,Smad3 mRNA的表达水平均明显高于假手术组(P<0.01),Smad7的表达低于假手术组(P<0.01);丹皮酚各剂量干预组Smad2,Smad3 mRNA的表达明显低于模型组(P<0.01),Smad7 mRNA的表达则明显强于模型组(P<0.01)。结论:丹皮酚有抗AMI大鼠心肌纤维化的作用,其机制与上调TGF-β1抑制性信号蛋白Smad7的mRNA表达及下调TGF-β受体调控信号蛋白Smad2,Smad3的mRNA表达有关。即其作用机制可能与干预TGF-β/Smads信号转导有关。

Objective：To discuss the protective effect of paeonol on ventricular remodeling in acute myocardial infarction （AMI） rats and to investigate its influence on Smad2,Smad3,Smad7 mRNA expression of TGF-β/Smads signaling pathway.Method：In vivo model of AMI was made using the left anterior descending coronary branch ligation.The rats were randomly divided into the model group,the sham group,the low-,mediumand high-dose paeonol groups （8,12,16 mg ·kg^-1）,and the captopril group （10 mg·kg^-1 based on ECG evaluation.The heart weight index and infarct size were measure after 4 weeks.The mRNA expression levels of Smad2,Smad3,Smad7 in myocardial tissues were detected using real-time quantitative （RT-qPCR） technique.Result：Compared with the model group,the myocardial infarct size was significantly reduced （P 〈 0.05）,the heart weight index decreased （P 〈 0.05） in all dose paeonol and captopril groups.Compared with the sham group,Smad2 and Smad3 mRNA expression levels were significantly higher,Smad7 expression level was lower in the model group （P 〈 0.01）.While,Smad2 and Smad3 mRNA expression levels decreased significantly,Smad7 expression level increased significantly in all dose paeonol groups （P 〈 0.01）.Conclusion：Paeonol has antimyocardial fibrosis effect in AMI rats.Its mechanism may be related to increasing the Smad7 mRNA expression of TGF-β 1 inhibitory signaling protein,and down-regulating the Smad2 and Smad7 mRNA expressions of TGF-β receptor signaling protein.