乙双吗啉降低阿霉素心脏毒性的实验研究

PREVENTIVE EFFECT OF BIMOLANE (AT-1727) ON THE CARDIO-TOXICITY INDUCED BY DOXORUBICIN IN MICE

在正常昆明小白鼠观察乙双吗啉对阿霉素所诱导的心脏毒性的影响,发现给小白鼠腹腔注射阿霉素1.5mg/kg,隔天一次,连用5次,继之剂量增至3mg/kg,隔天一次,亦连用5次时,光镜下10例有8例出现明显心脏病变,其中6例表现大片心肌纤维萎缩,其中2例分别为中度及轻度心肌纤维萎缩,电镜检查发现肌原纤维明显变窄,肌微丝排列紊乱,线粒体肿胀,少而短,或出现空泡。然而若于每次注射阿霉素前一天予先口服乙双吗啉10mg/kg,则光镜下11例仅6例出现轻度及中度心肌纤维萎缩,但无大片心肌纤维萎缩,经Ridit分析,差异显著(P<0.05)。电镜检查,合用组的心肌病变亦明显减轻。实验结果提示,乙双吗啉可预防阿霉素的心脏毒性。

A study on the preventive effect of bimolane (AT-1727) against the cardiotoxicity produced by doxorubicin in mice was caried out. Among 10 mice given do xorubicin alone, severe cardiac lesions (lesion score 3+) were observed light microscopically in 6 mice, moderate and mild lesions (lesion score 2+ and 1 + ) in each of the other two mice. Among 11 mice given doxorubicin and pretreated with bimolane, mild and mode-derate cardiac lesion was observed in 4 and 2 mice respectively, but no severe cardiac lesion (3+) was found in the combination group. By Ridit analysis, the difference between these two groups was statistically significant. Electron-microscopically, the atrophy of cardiac my-ofibrillae, disorderly arrangement of myofilaments, swelling and vacuolization of the mitochondria were noted in the heart muscle of mice treated with doxorubicin alone. Animals re-cieving the combimation of bimolane and doxorubicin showed a marked reduction in the severity of cardiopathy. The results of this study suggested that bimolane can ameliorate the cardiotoxicity induced by doxorubicin.