法舒地尔对异丙肾上腺素诱导大鼠心肌肥厚的干预作用及其机制

doi:10.13459/j.cnki.cjap.2016.05.008

中国应用生理学杂志 ›› 2016, Vol. 32 ›› Issue (5): 414-418.doi: 10.13459/j.cnki.cjap.2016.05.008

法舒地尔对异丙肾上腺素诱导大鼠心肌肥厚的干预作用及其机制

程杰坤, 孙小慧, 高莉萍, 李乐

浙江工业大学药学院, 杭州 310014

收稿日期:2015-07-07 修回日期:2016-05-12 出版日期:2016-09-28 发布日期:2018-06-20
通讯作者: 李乐,Tel:0571-88320535;E-mail:lile_1856@163.com E-mail:lile_1856@163.com
基金资助:
浙江省自然科学基金资助项目（LY13H310005）；浙江工业大学药学院华海基金资助项目（2011600049/028）

Effects of fasudil on isoproterenol induced cardiac hypertrophy in rats

CHENG Jie-kun, SUN Xiao-hui, GAO Li-ping, LI Le

College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China

Received:2015-07-07 Revised:2016-05-12 Online:2016-09-28 Published:2018-06-20
Supported by:
浙江省自然科学基金资助项目（LY13H310005）；浙江工业大学药学院华海基金资助项目（2011600049/028）

摘要/Abstract

摘要： 目的：研究法舒地尔对异丙肾上腺素诱导大鼠心肌肥厚的影响及其机制。方法：除正常对照组外，其它SD大鼠均皮下注射异丙肾上腺素（Iso，5 mg/kg）建立心肌肥厚模型。大鼠随机分为4组：正常对照组、Iso模型组、法舒地尔低剂量组（Fas，5 mg/kg，i.p）和法舒地尔高剂量组（Fas，20 mg/kg，i.p），连续给药8周。给药结束后，血流动力学检测大鼠心率（HR）、左心室收缩压（LVSP）、左心室末舒张压（LVEDP）和左室压力变化最大速率（±dp/dt_max）；分别测定大鼠体重（BW），心脏重量（HW），并计算HW/BW；大鼠心肌HE、Masson染色观察组织病理学改变；免疫组化法观察大鼠心肌组织ERK1、ERK2蛋白表达，RT-PCR观察ERK1、ERK2 mRNA的表达。结果：Iso模型组HR和LVEDP明显升高，LVSP和±dp/dt_max明显下降；HW/BW增大；心肌细胞体积变大，排列紊乱，胶原纤维增生；左心室组织ERK1、ERK2蛋白与mRNA表达上调。法舒地尔不同剂量干预后，心脏收缩和舒张能力得到改善，心指数明显下降，心肌细胞体积变小，纤维化减少，ERK1/2 mRNA表达下调，心肌组织损害均得到不同程度改善。结论：ERK1/2信号通路活化参与了异丙肾上腺素诱导的心肌肥厚，法舒地尔对异丙肾上腺素诱导的心肌肥厚具有明显改善作用，这可能与法舒地尔阻断ERK1、ERK2通路活化有关。

关键词: 异丙肾上腺素, ERK1/2, 法舒地尔, 心肌肥厚, 大鼠

Abstract: Objective: To investigate the effects and mechanisms of fasudil (Fas) on cardiac hypertrophy (CH) induced by isoprenaline(Iso) in rats. Methods: Except for the normal control group, the rest three groups rats were injected subcutaneously with Iso(5mg/kg) for setting up CH model. SD rats were randomly divided into four groups:Normal control group, Iso model group, Fas with low-dose group (5 mg/kg, i.p) and Fas with high-dose group (20 mg/kg, i.p). Animals were treated with Fas for 8 weeks. After the treatment, the following index were detected:heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), left ventricular systolic maximum rate (+dp/dt_max) and left ventricular diastolic maximum rate (-dp/dt_max). The body weight(BW) and heart weight (HW) were weighed and heart weight index (HWI) was calculateed. Myocardial tissue specimens, HE and Masson staining were performed for observing the histopathological changes. The protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2) in myocardial tissue was determined by using immunohistochemical methods. The expression of ERK1/2 mRNA in the myocardial tissue was detected by using semi-quantitative RT-PCR method. Results: Compared with normal control group, HR and LVEDP wereincreased significantly, while LVSP and ±dp/dtmax were decreased significantly; HWI was increased significantly in CH group; The myocardial cell volume and the cell gap were increased,cells arranged disorder, and severe myocardial interstitial fibrosis was presented in CH group. The expression of ERK1/2 mRNA was significantly increased. After Fas treatment, the systolic and diastolic functions of heart were improved, cell volume was reduced, cell gap became small, cells arranged in neat rows, and the fibrosis was significantly reduced. The expressions of RhoA, ERK1/2 mRNA were significantly reduced. The damages of myocardial tissue were improved in different degrees. Conclusion: ERK1/2 signaling pathway is involved in Iso induced CH. Fas protects against the CH of rats induced by Iso, which mechanisms may be related with blocking ERK1/2 signaling pathway.

Key words: isoproterenol, ERK1/2, fasudil, myocardial hypertrophy, rats

程杰坤, 孙小慧, 高莉萍, 李乐. 法舒地尔对异丙肾上腺素诱导大鼠心肌肥厚的干预作用及其机制[J]. 中国应用生理学杂志, 2016, 32(5): 414-418.

CHENG Jie-kun, SUN Xiao-hui, GAO Li-ping, LI Le. Effects of fasudil on isoproterenol induced cardiac hypertrophy in rats[J]. CJAP, 2016, 32(5): 414-418.

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法舒地尔对异丙肾上腺素诱导大鼠心肌肥厚的干预作用及其机制

Effects of fasudil on isoproterenol induced cardiac hypertrophy in rats

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