氢氯噻嗪和吲哒帕胺逆转自发性高血压大鼠心肌肥厚及促进心肌中内皮型一氧化氮合酶的表达

Effects of hydrochlorothiazide and indapamide on left ventricular hypertrophy and eNOS expression in spontaneous hypertensive rats

目的:研究氢氯噻嗪和吲哒帕胺对肥厚心肌及心肌中内皮型一氧化氮合酶(endothelialnitricox-idesynthase,eNOS)表达的影响,从而探讨其逆转心肌肥厚可能的分子机制。方法:15只成年雌性自发性高血压大鼠(SHR)随机分为对照组、氢氯噻嗪组、吲哒帕胺组。治疗前、开始至结束时每周测血压1次。4周后处死动物,取左心室称重后,计算左心室重与体重的比值,采用天狼猩红染色分析心肌间质和血管壁胶原分布。采用WesternBlot法检测心肌eNOS蛋白质表达。结果:治疗组动物收缩压及左心室重与体重比均明显低于对照组。心肌经天狼猩红染色后见治疗组心肌结构基本正常,与对照组相比未见明显的胶原沉积。并且治疗组在蛋白质水平显著上调心肌eNOS的表达(P<0.05)。结论:吲哒帕胺或氢氯噻嗪治疗自发性高血压可逆转左室肥厚、上调心肌eNOS、改善心肌纤维化从而起到保护心脏的作用。

AIM： To investigate the effects of hydrochlorothiazide and indapamide on cardiac remodeling and the expression of endothelial nitric oxide synthase （eNOS） in spontaneous hypertensive rats （SHR）. METHODS： Fifteen female SHRs were randomly divided into 3 groups （ n = 5） ： control group, hydrochlorothiazide （ HCTZ, 10 mg· kg^- 1· d^- 1 ） group and indapamide （ IND, 0. 625 mg· kg^- 1· d^- 1 ） group. Systolic blood pressure （SBP） of the rats in each group was measured at pretreatment and each week during the study. Four weeks later, rats were sacrificed and the ratio of heart weight to body weight was calculated, collagen deposition in the heart was determined histochemically using Sirius red staining, and eNOS protein expression of the heart was determined by Western blot. RESULTS： Both HCTZ and IND reduced the SBP of SHRs significantly （ P 〈 0.05 ）. The drug group showed normal myocardium structure as compared with control rats which showed myocardium cell hypertrophy, derangement, interstitial proliferation and mass collagen deposition. HCTZ and IND increased the eNOS expression significantly. CONCLUSION： Both HCTZ and IND can protect the heart by reversing cardiac remodeling, upregulate the eNOS expression and reduce collagen deposition.