基于RhoA/ROCK通路研究天麻素对高血压病左心室肥厚大鼠心室重构的影响
Effect of Gastrodin on Ventricular Remodeling in Hypertensive Rats with Left Ventricular Hypertrophy: A Study Based on the RhoA/ROCK Pathway
  
DOI:
中文关键词:  天麻素  左心室肥厚  信号通路  RhoA  ROCA  心室重构
英文关键词:Gastrodin  Left ventricular hypertrophy  Signaling pathway  Ras homolog gene family, member A  Rho-associated kinase  Ventricular remodeling
基金项目:中国中医科学院广安门医院南区院级科研基金项目(Y2014-06)
作者单位
侯玮琼,姜 北,赵 岩,杨勋超,毛文超,吴欣芳 中国中医科学院广安门医院南区内一科北京 102618 
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中文摘要:
      目的 观察天麻素对高血压病左心室肥厚大鼠心室重构的影响,从Ras同族体基因家族成员A(Ras homolog gene family member A,RhoA)/Rho激酶(Rho-associated kinase,ROCK)通路探究其作用机制。方法 将100只SD雄性大鼠随机分为假手术组,模型组,天麻素低剂量(16 mg/kg)、中剂量(24 mg/kg)、高剂量(32 mg/kg)组和依那普利组(1.5 mg/kg),每组15只。采用腹主动脉缩窄法复制左心室肥厚模型。采用酶联免疫吸附法测定大鼠血清血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)和白细胞介素6(interleukin-6,IL-6)水平,计算左心室肥厚指数(left ventricular hypertrophy index,LVHI);苏木精-伊红染色和Masson染色观察心肌的组织形态学变化;qRT-PCR和Western blot法检测心肌组织RhoA、ROCK mRNA及蛋白表达水平。结果 与假手术组比较,模型组大鼠尾动脉收缩压、LVHI及血清AngⅡ、IL-6水平显著升高(P<0.05),心肌组织纤维化程度升高,RhoA、ROCK mRNA及蛋白表达水平均显著升高(P<0.05)。与模型组比较,天麻素低、中、高剂量组和依那普利组尾动脉收缩压、LVHI及血清AngⅡ、IL-6水平均显著下降(P<0.05),心肌纤维程度降低,RhoA、ROCK mRNA及蛋白表达水平均显著降低(P<0.05)。依那普利组大鼠心肌组织RhoA、ROCK mRNA及蛋白表达水平最低,天麻素的作用具有剂量依赖性。结论 天麻素能有效降低高血压病大鼠尾动脉血压、LVHI和血清AngⅡ、IL-6水平,改善其心室重构,其机制与抑制RhoA/ROCK信号通路有关。
英文摘要:
      Objective To investigate the effect of gastrodin on ventricular remodeling in hypertensive rats with left ventricular hypertrophy (LVH) and its mechanism of action based on the Ras homolog gene family, member A (RhoA)/Rho-associated kinase (ROCK) pathway. Methods A total of 100 male Sprague-Dawley rats were randomly divided into sham-operation group, model group, low-, middle-, and high-dose gastrodin groups (at doses of 16, 24, and 32 mg/kg, respectively), and enalapril group (1.5 mg/kg), with 15 rats in each group. A rat model of LVH was established by the abdominal aorta constriction method. ELISA was used to measure the serum levels of angiotensin Ⅱ (AngⅡ) and interleukin-6 (IL-6); left ventricular hypertrophy index (LVHI) was calculated; hematoxylin and eosin staining and Masson staining were used to observe histomorphological changes of the myocardium; qRT-PCR and Western blot were used to measure the mRNA and protein expression of RhoA and ROCK in myocardial tissue. Results Compared with the sham-operation group, the model group had significant increases in systolic pressure of the caudal artery, LVHI, and serum levels of AngⅡ and IL-6 (P<0.05), a higher degree of myocardial fibrosis, and significant increases in the mRNA and protein expression levels of RhoA and ROCK (P<0.05). Compared with the model group, the low-, middle-, and high-dose gastrodin groups and the enalapril group had significant reductions in systolic pressure of the caudal artery, LVHI, and serum levels of AngⅡ and IL-6 (P<0.05), a lower degree of myocardial fibrosis, and significant reductions in the mRNA and protein expression levels of RhoA and ROCK (P<0.05). The enalapril group had the lowest mRNA and protein expression levels of RhoA and ROCK in myocardial tissue, and gastrodin exerted an effect in a dose-dependent manner. Conclusion Gastrodin can effectively reduce blood pressure of the caudal artery, LVHI, and serum levels of AngⅡ and IL-6 and improve ventricular remodeling in hypertensive rats, possibly by inhibiting the RhoA/ROCK signaling pathway.
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