【摘要】 目的探讨卡维地洛(Carvedilol,Car)、缬沙坦(Valsartan,Val)及其合用对自发性高血压大鼠(SHR)心肌细胞凋亡、心肌Bcl-2、P53蛋白表达的影响。方法6周龄雄性SHR24只,随机分为4组(n=6):一组为对照组,其他3组为干预组,分别予NS5ml、Cal(20mg·kg-1·d-1)、Val(40mg·kg-1·d-1)和Car+Val合用(剂量同上)干预8周后,予2%戊巴比妥钠40mg/kgIP麻醉、开胸取心脏,取左心室游离壁心肌于10%中性福尔马林中固定24小时,继之脱水,石蜡包埋及切片,采用TUNEL法、免疫组化法分别检测心肌细胞凋亡率(cardiacmyocyteapoptosisrate,CMAR),Bcl-2及P53蛋白表达率。结果与对照组比较,各干预组CMAR及P53蛋白表达率均明显降低,而Bcl-2蛋白表达率却明显增高,尤以合用组更明显(P<0.01)。与Car组、Val组比较,合用组CMAR及P53蛋白表达率均降低,而Bcl-2蛋白表达率均增高(P<0.01)。与Car组比较,Val组CMAR、Bcl-2及P53蛋白表达率,差异无显著性意义(P>0.05)。各组中P53蛋白表达率与CMAR呈正相关;而Bcl-2与CMAR呈负相关((P<0.05)。结论CarVal均可抑制SHR心肌细胞凋亡,二者合用效应更明显,可能与两药均能上调BCL-2蛋白表达和下调P53蛋白表达有关。更多还原

【Abstract】 Objective To explore the effects of Carvedilol, Valsartan on cardiacmyocyte apoptosis, and the expression rate of Bel-2 and P53 proteins of myocytes in spontaneously hypertensive rats (SHR). Methods 24 males 6-week-old SHRs were randomly divided into four groups: One group as control group, else groups as interfered groups. Four groups were respectively administrated NS 5ml. d1, Car 20mg. kg-1. d-1, Val 40 mg. kg-1. d-1 and Car 20 mg. kg-1. d-1 +Val 40 mg. kg - 1. d-1 by stomach filling for 8 week Thereafter all SHRs were anesthetizing by pentobarbital(40 mg. kg-1, ip) and cut the free wall of left ventricle by thoracectomy and detected cardiacmyocyte apoptosis rate (CMAR) and the expression of Bcl-2 and p53 protein in myocardium by TUNEL and im-munohistochemical technique. Results Compared with the control, CMAR and the expression rate of P53 protein were significantly decreased, the expression rate of BCL-2 protein was significantly increased in each of interfered group. Correlation analysis suggested that CMAR was positive correlation with the expression rate of P53 protein, and a negative correlation with BCL-2 protein in each of group. Conclusion Carvedilol and Valsartan could obviously inhibit the cardiacmyocyte apoptosis, and the effect was more obvious by combined the two drugs , it was possibly correlative that the two drugs could increase the expression of bcl-2 protein and decrease the expression of P53 protein.更多还原