心肌肥厚的PTEN负性调控与卡托普利干预对其影响的实验研究  

PTEN negatively regulates isoproterenol-induced cardiac hypertrophy and effects of captopril on PTEN expression

作　　者：周裔忠[1] 祝善俊[1] 于林君[1] 田颖[1] 王江[1] 

机构地区：[1]第三军医大学新桥医院心血管内科,重庆400037

出　　处：《中华心血管病杂志》2005年第8期738-742,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目(30370584)

摘　　要：目的检测异丙肾上腺素(isoproterenol,ISO)诱导的心肌肥厚大鼠PTEN mRNA、蛋白水平表达及卡托普利(captopril,Cap)对其表达的影响,从而探讨PTEN的负性调控在心肌肥厚中的作用。方法24只大鼠随机分为对照组、ISO组、Cap+ISO组。利用小剂量ISO持续背部皮下注射大鼠,建立心肌肥厚模型。在观察期末,分别测定各组大鼠体重、心脏湿重、左室湿重,计算出心脏重量/体重及左室重量/体重;电镜观察超微结构的变化,并测定左室收缩末压、左室舒张末压、左心室压力上升及下降最大速率等指标。RT-PCR测定心肌组织PTEN mRNA,Western blot测定其蛋白表达。结果(1)与对照组比较,ISO组、Cap+ISO组的左室重量/体重、心脏重量/体重、左室收缩末压、左室舒张末压均升高(P≤0.05),左室压力上升及下降最大速率(±dp/dtmax)均下降(P≤0.05)。(2)与ISO组相比,Cap+ISO组的左室重量/体重、心脏重量/体重、左室收缩末压、左室舒张末压均下降(P≤0.05,P≤0.01),左室压力上升及下降最大速率(±dp/dtmax)均升高(P≤0.05,P≤0.01)。(3)与对照组比较,ISO组、Cap+ISO组的PTEN mRNA、蛋白表达均增加。(4)与ISO组比较,Cap+ISO组的PTEN mRNA、蛋白表达增加。结论ISO诱导心肌肥厚PTENmRNA、蛋白表达升高,心肌肥厚过程中存在负性调控,PTEN是一种内源性抑制心肌肥厚的重要因子。卡托普利不仅能明显抑制心肌肥厚,改善血液动力学参数,而且还能上调心肌PTEN水平,这是其抑制心肌肥厚的又一机制。Objective To examine the negative regulation role of PTEN in isoproterenol-induced cardiac hypertrophy by testing the expression of PTEN mRNA and protein and to explore the effects of captopril （Cap）on PTEN expression. Methods Twenty four rats were randomly divided into three groups： control group, ISO group, and ISO ＋ Cap group. The following parameters were examined： body weight （BW） , heart weight （HW） , left ventricular weight （LVW） , left ventricular end-diastolic pressure （ LVEDP ） , left ventricular end-systolic pressure （ LVESP ） and ＋ dp/dtmax. The ratio of HW/BW and LVW/BW was calculated. PTEN mRNA and protein were tested by RT-PCR and Western blot, respectively. Results （ 1 ） Compared with the control group, the ratio of HW/BW and LVW/BW, LVEDP and LVESP were all increased in ISO group and ISO ＋ Cap group （ P 〈 0.05 ）, but ＋ dp/dtmax was decreased （ P 〈 0. 05 ） ; （ 2 ） compared with the ISO group, the ratio of HW/BW and LVW/BW, LVEDP, LVESP were all decreased in ISO ＋ Cap group （ P 〈 0.05 ） , but ＋ dp/dtmax was increased （ P 〈 0.05 ） ;（ 3 ） compared with the control group, PTEN mRNA and protein were up-regulated in ISO group and ISO ＋ Cap group; （4） compared with the ISO group,PTEN mRNA and protein were up-regulated in ISO ＋ Cap group. Conclusions PTEN mRNA and protein are up-regulated in isoproterenol-induced cardiac hypertrophy. Captopril can up-regulate PTEN expression in cardiac hypertrophy. There is a negative regulative mechanism in cardiac hypertrophy process, in which PTEN is probably an endogenous negative regulator of cardiac hypertrophy.

关 键 词：心肌肥厚 基因表达调控 卡托普利 异丙肾上腺素 PTEN PTENMRNA 心肌肥厚模型 负性调控 实验研 左室舒张末压 

分 类 号：R542.22[医药卫生—心血管疾病]