p53-Bcl-2/Bax凋亡信号通路变化在自发性高血压大鼠左心室重构进程中作用（英文）

p53-Bcl-2/Bax apoptosis signal pathway plays a key role in left ventricular remodeling of spontaneously hypertensive rats

目的通过观察自发性高血压大鼠(SHR)左心室病理形态、心肌细胞凋亡及相关凋亡蛋白p53、Bcl-2、Bax表达水平的动态变化,揭示SHR左心室重构的机制。方法将13周龄雄性SHR和WKY大鼠适应性喂养1周后随机分为6组,分别饲养至第18、22、26周龄取材备用(n=4)。魏-凯二氏大鼠(WKY)为正常对照组。期间每4周采用CODA Kent法测定大鼠尾部血压,用HE染色和TUNEL染色观察大鼠左心室组织病理形态及心肌凋亡的动态变化。用Western blot分析左心室p53、Bcl-2及Bax蛋白表达的变化。结果第18、22、26周龄WKY组大鼠的上述各项指标均未随周龄的增长而变化。相比同周龄WKY组,第18、22、26周龄SHR组大鼠的收缩压及舒张压明显升高(P<0.05),左室病理重构及心肌细胞凋亡明显;p53、Bax蛋白水平显著升高,Bcl-2蛋白水平及Bcl-2/Bax蛋白比值显著降低(P<0.05)。与第18周龄SHR组相比,第22周龄SHR组和第26周龄SHR组的左室病理重构和心肌细胞凋亡明显增加,Bcl-2水平及Bcl-2/Bax蛋白比值明显降低,p53、Bax蛋白水平均显著升高(P<0.05)。而与第22周龄SHR组相比,第26周龄SHR组大鼠的上述指标的差异更加明显。结论随着周龄的增加,不同周龄SHR组大鼠左室重构明显,心肌细胞凋亡率、p53、Bax表达水平逐渐增加,Bcl-2水平及Bcl-2/Bax蛋白比值逐渐降低,提示左室重构的机制可能与p53-Bcl-2/Bax通路介导的心肌细胞凋亡有关。

Objective To reveal the underlying mechanism of left heart ventricular remodeling in spontaneously hypertensive rats through observing dynamic changes of the left ventricular pathological morphology,myocardial appoptosis,and proteins expressions of p53,Bcl-2 and Bax.Methods Male spontaneously hypertensive rats(SHR) and wistar-kyoto rats(WKY) at 13 th week of age were adaptive fed for 1 week,then randomly divided into six groups.Rats in each group were fed to 18 th,22 th and 26 th week-age(n=4) and left heart tissues were collected,respectively.During the period,rat tail blood pressure was tested by the Scientific CODA Kent method once four weeks,and the left ventricular tissue was taken to observe the changes of the pathological morphology and myocardial appoptosis via HE and TUNEL staining,respectively.The left ventricular tissue protein levels of p53,Bcl-2 and Bax were performed by western blot assay.Age-matched WKY were conducted as the normal control group.Results The above indexes of rats in WKY group had no significant changes as the increase of week-age.Compared with the age-matched WKY group,systolic blood pressure and diastolic pressure in rats of SHR group were increased.Left ventricular pathological remodeling and the apoptosis of cadiomyocytes were observed in rats of SHR group.The protein levels of p53 and Bax were increased,while the protein level of Bcl-2 and the ratio of Bcl-2/Bax were decreased.Compared with that of SHR 18 week-age group,the protein expression of Bcl-2 and the ratio of Bcl-2/Bax were reduced,other proteins expression of rats in SHR22 week-age and SHR 26 week-age group were increased.In addition,left ventricular pathological remodeling and the apoptosis of cadiomyocytes became more obvious.Compared with the SHR 22 week-age group,the above indexes of rats in SHR 26 week-age were aggravated.Conclusion The degree of left ventricular remodeling and apoptosis of cadiomyocytes,protein expressions of p53,Bcl-2 and Bax of rats in SHR are closely related to age,suggesting that p53-Bcl-2/Bax signal pathway-induced apoptosis is involved in left ventricular remodeling.