卡维地洛对乳鼠心肌细胞缺氧／复氧损伤的抗凋亡作用  

Carvedilol antagonizes hypoxia/reoxygenation-induced apoptosis in cultured neonatal rat cardiomyocytes

作　　者：沈晓咏[1] 肖明第[2] 杨迪成[2] 

机构地区：[1]复旦大学附属华东医院胸外科,上海200040 [2]上海交通大学附属第一人民医院心外科

出　　处：《上海医学》2008年第3期184-186,F0003,共4页Shanghai Medical Journal

摘　　要：目的研究卡维地洛对缺氧/复氧损伤心肌细胞的抗凋亡作用,并探讨其可能的作用机制。方法新生1～3 d的SD鼠,原代分离,培养其心肌细胞72 h后随机分成正常对照、单纯缺氧/复氧及卡维地洛+缺氧/复氧组。使培养板中的细胞缺氧(氧浓度<1%)120 mm,复氧30 min,制造缺氧/复氧损伤模型。观察卡维地洛对缺氧/复氧心肌存活率及Bcl-2、Bax蛋白表达情况的影响。结果卡维地洛+缺氧/复氧组心肌细胞存活率为(70.21±2.12)%,显著高于单纯缺氧/复氧组的(58.39±3.22)%(P<0.05);卡维地洛+缺氧/复氧组Bcl-2蛋白表达为(12.22±1.62)%,与单纯缺氧/复氧组(20.32±3.62)%的差异无统计学意义(P>0.05);卡维地洛+缺氧/复氧组Bax蛋白表达为(32.62±4.22)%,显著低于缺氧/复氧组的(40.21±3.22)%(P<0.05);卡维地洛+缺氧/复氧组Bcl-2/Bax比值为0.62,显著高于缺氧/复氧组的0.30(P<0.05)。结论卡维地洛有显著抗缺氧/复氧损伤后心肌细胞凋亡的作用,其作用机制可能与抑制缺氧/复氧损伤的心肌细胞Bax表达,使Bcl-2/Bax比值升高有关。Objective To observe the effects of carvedilol against hypoxia/reoxygenation-induced apoptosis in cultured neonatal rat cardiomyocytes and explore its possible mechanism. Methods The cardiomyocytes isolated and purified from neonatal SD rats （1 to 3 days old） were cultured for 72 h and divided into the control group, hypoxia/reoxygenation group, and carvedilol-pretreated hypoxia/reoxygenation group. Hypoxia/reoxygenation model was established by exposing the cardiomyocytes to anoxia for 120 rain followed by reoxygenation for 30 min. The protective effect of carvedilol on cardiomyocyte survival after hypoxia/reoxygenation exposure was evaluated, and its effect on Bcl-2 and Bax expression in the cardiomyoctyes was assessed using immunohistochemistry. Results The viable cell percentage in the carvedilol-pretreated hypoxia/reoxygenation group was （70.21±2.12） %, significantly higher than that of （58.39±3.22） % in the hypoxia/reoxygenation group. Immunohistochemistry demonstrated no significant difference in Bcl 2 expression between the carvedilol-pretreated group and the hypoxia/reoxygenation group （[12.22±1.62]% vs [20.32±3.62]%, P〉0.05）, but the carve dilol-pretreated cells showed significantly lowered Bax expression [ （32.62 ± 4.22）% vs （40.21 ± 3.22） %, P〈 0.05], resulting in significant difference in the Bcl-2/Bax ratio between the two groups （0.62 vs 0. 30, P〈 0. 05）. Conclusion Carvedilol can significantly reduce cardiomyocyte apoptosis in response to hypoxia/reoxygenation exposure, possibly by inhibiting Bax expression to increase of Bcl-2/Bax ratio in the cardiomyocytes.

关 键 词：卡维地洛 缺氧/复氧 细胞凋亡 基因表达 

分 类 号：R96[医药卫生—药理学]