天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (4): 449-452.doi: 10.11958/20150146

• 实验研究 • 上一篇    下一篇

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

聂丹1 ， 孙红丹1 ， 时召平2 ， 周晓慧1△   

  1. 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 （邮编067000）； 2承德市中医院药剂科
  • 收稿日期:2015-09-06 修回日期:2015-11-10 出版日期:2016-04-15 发布日期:2016-05-20
  • 通讯作者: △通讯作者 E-mail： zxh5055@sina.com E-mail:18729542245@163.com
  • 作者简介:聂丹 （1991）， 女， 硕士在读， 主要从事心血管药理学研究
  • 基金资助:
    河北省自然科学基金项目 （C2011406009）； 河北省教育厅重点项目 （Z20131068）

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

NIE Dan1 , SUN Hongdan1 , SHI Zhaoping2 , ZHOU Xiaohui 1△   

  1. 1 Key Laboratory of Study and Exploiture for New Drugs of Traditional Chinese Medicine (TCM)， Institute of TCM Medical of Chengde Medical College， Chengde 067000， China； 2 Chengde Traditional Chinese Medicine Hospital
  • Received:2015-09-06 Revised:2015-11-10 Published:2016-04-15 Online:2016-05-20
  • Contact: △Corresponding Author E-mail： zxh5055@sina.com E-mail:18729542245@163.com

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摘要： 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。

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

Abstract: Abstract: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 mechanism thereof. 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), left ventricular 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 Smad2/3 were detected by Western blot assay. Results There were significant differences in parameters used for detecting treatment group 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 Smad2/3 were significantly decreased in formula group than those of PAE group and PNS group, and lower levels in formula high dose group 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.

Key words: myocardial infarction, disease models, animal, ventricular remodeling, transforming growth factor beta, drug therapy, combination, Smad2/3, compound of Paeonol and PNS