丹皮酚、三七总皂苷组方对心肌梗死后心室重构大鼠TGF-β/Smads信号通路的影响  

The effects of combination of paeonol and PNS on TGF-β/Smad pathway in ventricular remodeling after myocardial infarction in rats

作　　者：聂丹[1] 孙红丹[1] 时召平 周晓慧[1] 

机构地区：[1]承德医学院中药研究所河北省中药研究与开发重点实验室,067000 [2]承德市中医院药剂科

出　　处：《天津医药》2016年第4期449-452,I0002,共5页Tianjin Medical Journal

基　　金：河北省自然科学基金项目(C2011406009);河北省教育厅重点项目(Z20131068)

摘　　要：目的探讨丹皮酚、三七总皂苷组方对心梗后心室重构大鼠转化生长因子(TGF)-β/Smads信号通路的影响及可能机制。方法通过结扎左冠状动脉前降支制造大鼠急性心肌梗死模型,依干预方式不同分为模型组、丹皮酚(8 mg·kg-1)组、三七总皂苷(40 mg·kg-1)组、组方低剂量组(丹皮酚4 mg·kg-1+三七总皂苷20 mg·kg-1)、组方高剂量组(丹皮酚8 mg·kg-1+三七总皂苷40 mg·kg-1),卡托普利组(10 mg·kg-1)。另设假手术组,只穿线不结扎。连续给药28 d后检测左心室收缩压(LVSP)、左心室舒张压(LVEDP)、左心室内最大上升和下降速率(±dp/dtmax);HE染色观察各组大鼠心肌病理学变化;Western blot检测TGF-β1、Smad2/3蛋白的表达。结果用药组与模型组比较,组方组与中药单药组比较,组方高剂量组与组方低剂量组比较,各指标变化均较明显,差异均有统计学意义(P<0.01)。模型组呈病理改变,各用药组均有不同程度的病理结构改善;组方组和卡托普利组改善最明显。与模型组比较,各用药组TGF-β1、Smad2/3蛋白表达较模型组降低,组方组较丹皮酚组和三七总皂苷组降低;组方高剂量组较组方低剂量组降低(均P<0.01)。结论丹皮酚、三七总皂苷组方可抑制心肌梗死后心室重构大鼠心肌组织TGF-β1、Smad2/3的蛋白表达,有明显协同作用,其机制可能是通过阻断TGF-β/Smads信号通路实现的。Objective To study the effect of paeonol（PAE） and PNS on the expression of transforming growth factor（TGF）- beta 1/ Smad2/3 pathway in rats with acute myocardial infarction（AMI）, and the possible molecular mechanismthereof. Methods Model of AMI was made using left anterior descending coronary branch ligation. According to the inter-vention methods rats were divided into model group, PAE group（8 mg·kg-1）, PNS group（40 mg·kg-1）, PAE（4 mg·kg-1） ＋PNS（20 mg·kg-1） low dose group, PAE（8 mg·kg-1） ＋ PNS（40 mg·kg-1） high dose group and captopril positive control group（10 mg·kg-1）. Rats without ligation were used as Sham operation group. Left ventricular systolic blood pressure（LVSP）, leftventricular diastolic pressure（LVEDP） and the maximum rise and fall rate（/dtmax DP） were detected after 28-day treat-ment. HE staining was used to observe changes of myocardial tissue. The protein expression levels of TGF-β1 and Smad2/3were detected by Western blot assay. Results There were significant differences in parameters used for detecting treatmentgroup and model group, formula group and single drug group, formula high dose group and formula low dose group（P 0.01）. The model group showed pathological changes. All treatment groups showed different degrees of pathological improve-ment. There was the most significant improvement in formulae group and captopril group. Compared with the model group,TGF-β1 and Smad2/3 protein expressions were decreased in treatment group. The expression levels of TGF-β1 and Smad2/3were significantly decreased in formula group than those of PAE group and PNS group, and lower levels in formula high dosegroup than those of formula low dose group（P 0.05）. Conclusion Paeonol and PNS can inhibit the expressions of TGF-β/Smad 2/3 protein in rats with AMI, by blocking TGF-β / Smad pathway.

关 键 词：心肌梗死 疾病模型 动物 心室重构 转化生长因子β 药物疗法 联合 SMAD2/3 丹皮酚、三七总皂苷组方 

分 类 号：R542.22[医药卫生—心血管疾病] R969.3[医药卫生—内科学]