摘要
目的探讨卡维地洛对自发性高血压大鼠(SHR)心肌细胞凋亡、心肌Bcl2、p53蛋白表达、血浆超氧化物歧化酶(SOD)、丙二醛(MDA)及血管紧张素Ⅱ(AngⅡ)水平的影响。方法6周龄雄性SHR12只,随机分为2组(n=6):对照组:普通饲料喂养+NS5mL/d灌胃;卡维地洛组:卡维地洛(Car)20mg/(kg·d)+NS5mL溶解灌胃,其余同对照组,共8周。随后给予2%戊巴比妥钠40mg/kgIP麻醉,剖腹取下腔静脉血3mL,分3等分于试管中分离血浆保存,待测AngⅡ、SOD与MDA。继之开胸取心脏,取左心室游离壁心肌于10%中性福尔马林中固定24h,继之脱水,石蜡包埋及切片,并采用TUNEL法、免疫组化法分别检测心肌细胞凋亡率,Bcl2及p53蛋白表达率。结果与对照组比较,Car组血浆MDA、AngⅡ、心肌细胞凋亡率及心肌细胞p53蛋白表达率均明显降低,而血浆SOD、心肌细胞Bcl2蛋白表达率则明显增高(P<0.01)。且两组中MDA、AngⅡ及p53蛋白表达率与心肌细胞凋亡率均分别呈正相关;而SOD、Bcl2蛋白表达率与心肌细胞凋亡率呈负相关(P<0.05)。结论Car具有明显抑制SHR心肌细胞凋亡,p53蛋白表达和抗氧化作用,同时还能明显改善Bcl2蛋白表达的效应,AngⅡ、p53蛋白表达、Bcl2蛋白表达和脂质过氧化反应均可能参与了心肌细胞凋亡过程。
ObjectiveTo explore the effects of carvedilol on cardiomyocyte apoptosis, the expression rate of Bcl-2 and p53 proteins of myocytes as well as SOD, MDA and Ang Ⅱ in serum in spontaneously hypertensive rats (SHR).MethodsTwelve 6-week-old SHRs were randomly to control group (NS 5 mL/d, ig n=6) and carvedilol (Car) group(20 mg/kg·d dissolved in NS 5 mL ig n=6).Eight weeks after treatment, serum superoxide dismutase(SOD), malondialdehyde(MDA) and angiotensin Ⅱ (Ang Ⅱ) were examined.Apoptosic rate and expression of Bcl-2 and p53 protein in myocardium were determined by TUNEL and immunohistochemical technique.ResultsCompared with the control,apoptosis rate, the expression of p53 protein of cardiomyocytes, MDA and Ang Ⅱ in serum were significantly decreased.The expression of Bcl-2 protein and SOD were significantly increased as compared with control(P<0.01).Correlation analysis suggested that the apoptosis rate of cardiomyocyte was positively correlated with p53 protein expression, MDA and Ang Ⅱ, and a negatively related with Bcl-2 protein expression and SOD in two groups (P<0.05).ConclusionCarvedilol substantially inhibits cardiomyocyte apoptosis and the expression of p53 protein and improves the expression of Bcl-2 protein.Ang Ⅱ, expression of p53 and Bcl-2 protein and lipid superoxide reaction might be involved in cardiomyocyte apoptosis.
出处
《高血压杂志》
CSCD
北大核心
2005年第6期368-371,共4页
Chinese Journal of Hypertension
