卡维地洛(Carve dilol)对心肌bcl-2、bax表达的影响  

The Effects of Carvedilol on the Gene Expression of bcl-2 and bax in Heart in Rats

作　　者：沈玉芹[1] 吕立夏[2] 邓兵[3] 戚秀卿[3] 邓南伟[3] 徐文渊[3] 

机构地区：[1]同济大学附属同济医院急诊科,上海200065 [2]同济大学医学院生化教研室,上海200092 [3]同济大学附属同济医院心内科,上海200065

出　　处：《高血压杂志》2004年第4期345-349,共5页Chinese Journal of Hypertension

摘　　要：目的　研究卡维地洛对心肌凋亡相关基因bcl 2、bax表达的影响。方法　SD大鼠随机分三组 :对照组 ,阿霉素组 ,阿霉素 +卡维地洛组。阿霉素腹腔注射 (2 0mg/kg)制备心肌毒性动物模型 ;卡维地洛组在注射阿霉素之后立即腹腔注射卡维地洛 (2mg/kg) ;等量生理盐水用于对照组。于用药后第 1,3,5 ,10 ,15d采用逆转录聚合酶链反应 (RT PCR)和免疫组织化学染色法检测心肌bcl 2、bax基因和蛋白水平表达的变化。结果　 (1)以GAPDH为内标 ,第 1、3、5、10d ,阿霉素组中bcl 2基因表达逐渐减弱 ,bax基因表达逐渐增强 ;阿霉素 +卡维地洛组中bcl 2表达逐渐增强 ,于第 5、10天bcl 2表达高于阿霉素组 ,bax表达逐渐减弱 ,于第 5、10天bax表达低于阿霉素组 ;(2 )阿霉素 +卡维地洛组Bcl 2、Bax阳性心肌细胞百分比较阿霉素组均有显著性差异 (P <0 0 5 )。结论　 (1)阿霉素心肌毒性与促进bax的表达同时抑制bcl\|2表达有关 ;(2 )卡维地洛可以促进bcl 2的表达 ,减弱bax的表达。提示卡维地洛的心肌保护作用可能通过差异调节bcl 2和bax的表达而实现。Objective To study the effects of carvedilol on the gene expression of bcl-2 and bax in heart in rats. Methods SD rats were divided into three groups: control group, adriamycin group, adriamycincarvedilol group. The models of myocardium toxicity were prepared using intraperitoneal injection of adriamycin (20 mg/kg); carvedilol (2 mg/kg) was injected intraperitoneally after adriamycin. The equivalent volume of normal saline was used as control. The heart tissues were obtained at the 1, 3, 5, 10, and 15 days after drug administration. Reverse transcription polymerase chain reaction and immunohistochemistry were performed to assess the expression in bcl-2 and bax genes at different time course in mRNA and protein levels. Results (1)mRNA expression level of bcl-2 showed a tendency of decrease while a tendency of increase of bax level in adriamycin group. On contrary, carvedilol reversed the tendency by significantly higher bcl-2 expression and lower level of bax. (2) With immunohistochemistry technique, there is a significant difference for percentage of bax and bcl-2 positive cells between adriamycin group and adriamycincarvedilol group respectively (P<0.05). Conclusion The toxicity of adriamycin may be mediated by up-regulation of bax and down-regulation of bcl-2, carvedilol may promote the expression of bcl-2 and inhibit the expression of bax. These data provide clues to elucidate the protective mechanism of carvedilol.

关 键 词：卡维地洛 CARVEDILOL bcl-2、bax 凋亡相关基因 心肌保护 

分 类 号：R965[医药卫生—药理学]