卡维地洛对阿霉素致心肌毒性的保护作用

Protective effects of carvedilol on rats cardiomyocytes exposed to adriamycin

目的研究卡维地洛对心肌bcl-2、bax、TNF-α、TNF-αR1蛋白的影响。方法SD大鼠随机分四组：正常对照组,阿霉素(ADR)组,阿霉素+卡维地洛(ADR+CARV)组,卡维地洛(CARV)组。阿霉素腹腔注射(累计15mg/kg,分6次注射)制备心肌毒性动物模型；ADR+CARV组在注射阿霉素之后立即腹腔注射卡维地洛(累计10mg/kg,分6次注射)；卡维地洛组(累计10mg/kg,分6次注射)；等量生理盐水用于对照组。于第三周第七天处死大鼠,采用Western blot方法。结果TNF-α、bcl-2的检测：ADR组条带明显；ADR+CARV组条带不明显或已消失；正常对照组和CARV组无条带。bax与TNF-αR1的检测：在检测膜上目标位置均未出现明显条带。结论卡维地洛能够抑制TNF-α的表达,增强bcl-2的表达,但对bax和TNF-αR1的表达作用不明显。从蛋白水平上再度证明卡维地洛能够增强bcl-2的表达,但对bax的表达作用不明显,迟于分子生物学水平的表达。在蛋白水平上表明：卡维地洛能够抑制TNF-α的表达,但对TNF-αR1的表达作用不明显,不同于分子生物学水平的表达。

Objective To study the protective effects of earvedilol on rats eardiomyoeytes exposed to adfiamyein. Methods SD rats were randomly divided into four groups： control group, adfiamyein group,adriamyein ＋ carvedilol group, earvedilol group. The models of myoeardium toxicity were prepared with intrapefitoneal injection of adriamyein （ total 15 mg/kg, injeetion by 6 times）;Carvedilol was applied intraperitoneally followed adriamyein administration with a dose of （ total 2mg/kg, injection by 6 times ） ;the equivalent volume of normal saline was used in control group. The heart tissues were obtained at the 21st day after the first time drug administration. The Western blot were performed to assess the expression alternation of bel - 2, bax,TNF -α and TNF -αR1 in protein levels. Results ①The expression of TNF-α showed clearly in adfiamyein group and obseurly or dispeared in, adriamycin ＋ earvedilol group, no sign in earvedilol group and control group. ②The expression of bcl - 2 showed clearly in earvedilol group and obseurly or dispeared in, adriamycin ＋ earvedilol group, no sign in adriamyein group and control group. Conlusions Carvedilol may promote the expression of bc1-2 and inhibit the expression of TNF-α,but there is no clear influence to bax and TNF-α R1 by earvedilol. Tthese data may provide useful clues to elueidating the protective mechanism of earvedilol in protein levels.