缬沙坦对自发性高血压大鼠心肌Bcl-2和Bax蛋白表达的影响

背景高血压的心肌肥厚(cardiomyopathyhypertrophy)是对于慢性动脉压力超负荷的一种代偿反应,压力负荷持续性增高将导致心肌收缩力下降.在心肌代偿性肥厚发展为心力衰竭机制的众多研究中,心肌细胞进行性丢失日益受到重视.目的探讨遗传性高血压及左室肥厚过程中心肌组织凋亡调节蛋白Bcl-2,Bax表达的变化及血管紧张素Ⅱ1型受体(angiotensinⅡtype1 receptor,AT1R)拮抗剂缬沙坦的影响.设计随机对照实验研究.单位一所大学医学院心内科,一所大学医院心内科.材料本实验在北京大学人民医院中心实验室完成.实验选用8周龄自发性高血压大鼠(SHR)30只,按随机数字法将其分为缬沙坦组和非治疗组;以8周龄Wistar鼠15只作为对照组.干预所有动物饲养8周,取左心室组织,称质量备用.部分心肌组织置100mL/L甲醛液中固定6 h后常规石蜡包埋备形态学研究.计算心脏指数.采用免疫组化、Western印迹等方法检测凋亡调节蛋白Bcl-2,Bax表达.主要观察指标心肌细胞Bcl-2及Bax蛋白Westernblot条带吸光度(A值)扫描值及Bcl-2/Bax比值.结果SHR心肌中存在Bax高表达,缬沙坦治疗8周后,SHR心肌组织Bax蛋白表达显著降低至接近对照组.缬沙坦组及对照组Bcl-2蛋白表达与非治疗组比较,差异无显著性意义(P＜0.05).缬沙坦组及对照组Bcl-2/Bax比值(6.71±1.10,5.86±0.70)明显高于非治疗组(0.63±0.23)(P＜0.05).结论心肌细胞凋亡是代偿性心肌肥厚发展为心力衰竭的可能机制之一.高血压早期缬沙坦在降压同时有效抑制心肌细胞凋亡.

Effect of valsartan onthe expressions of Bcl-2 and Bax proteins in myocardium of spontaneously hypertensive rats

BACKGROUND: An increase in cardiac work-load during hypertension promotes an adaptive response consisting of cardiomyocytes hypertro phy. Although this response is initially compensatory, continuing cardiac overload leads to a decreased global cardiac function and subsequently to heart failure, and among the mechanisms involved, that contributing to the progressive loss of cardiomyocytes has attracted more and more attention.OBJECTIVE: To explore the changes of the expressions of apoptosis regulating oncogene Bcl-2 and Bax in myocardial tissue during genetic hypertension and left ventricular hypertrophy, and evaluate the effect of valsartan, the antagonist to angiotensin Ⅱ type 1 receptor(AT1R) on the ratio of the Bcl-2/Bax.DESIGN: A randomized controlled study.SETTINGS: Cardiological department in a medical college of university anda university hospital.MATERIALS: The trial was completed in the Central Laboratory, People's Hospital of Peking University. Thirty spontaneously hypertensive rats(SHR)of 8 weeks old were divided into valsartan group and non-treated group according to the method of random number table, and another 15 Wistar rats of 8-week old were taken as the controls.INTERVENTIONS: All the rats were fed for 8 weeks, the left ventricular tissues were excised and weighed for later use. Part of the myocardial tissues were fixed in 100 mL/L buffered formalin for 6 hour, and were embedded by routine paraffin wax for morphological study. The cardiac index was calculated by cardiac mass/body mass. The expressions of apoptosis regulating Bcl-2 and Bax proteins were detected by immunohistochemistry and Western blot.MAIN OUTCOME MEASURES: Expressions of Bcl-2 and Bax protein as scanning band absorbance in Western blot, the ratio of Bcl-2/Bax.RESULTS: There was high expression of Bax protein in the myocardium of SHR, after valsartan treatment for 8 weeks, the expression of Bax protein in the myocardiun of SHR was significantly reduced to the level near to that in the control group. The expressions of Bcl-2 protein in the valsartan group and control group were insignificantly different from that in the non-treated group( P ＞ 0.05) . The ratios of bax/bcl-2 in the valsartan group(6.71± 1.10) and control group(5.86 ±0. 70) were obviously higher than that in the non-treated group(0. 63 ±0.23) ( P ＜ 0.05).CONCLUSION: Cardiac apoptosis is one of the possible mechanisms for compensatory myocardial hypertrophy developing into heart failure. Early valsartan treatment on hypertension has not only the effect of depression, but also can effectively inhibit myocardial apoptosis.