Dasmahapatra K S, Vezeridis M, Rao U, Perez-Brett R, Karakousis C P
J Surg Res. 1984 Mar;36(3):217-22. doi: 10.1016/0022-4804(84)90090-8.
Adriamycin (ADR) is a useful antitumor agent but causes severe cardiotoxicity requiring dose limitation. Methylprednisolone (MP) has been shown to stabilize cell membranes and, in ischemic heart models, to protect mitochondria lysosomes and sarcolemma. The purpose of this study was to determine if MP could prevent ADR-induced cardiotoxicity in rats. Twenty-eight normal, male, Wistar rats were placed in two groups of 14 each. One group received ADR 2 mg/kg iv weekly for 3 weeks, followed by 2 mg/kg subcutaneously weekly. The other group received the same dosage of ADR but also MP 20 mg/kg subcutaneously 3 hr before, with ADR and 3 hr after ADR. Seven rats in each group were sacrificed after the 10th week of treatment. At autopsy 7/7 (100%) of the rats in the ADR groups had obvious ascites and pleural effusion whereas 0/7 in the ADR + MP group developed this complication (P less than 0.01). Microscopic examination of the hearts revealed vacuole formation, loss of muscle mass, tapering off of myocardial cells, or inflammatory changes in 7/7 (100%) of the rats in the ADR group and in 2/7 (28%) of the ADR and MP group (P less than 0.05). Among the rats left to monitor survival, at 11 weeks from the initiation of treatment, 4/7 (57%) in the ADR group and 7/7 (100%) in the ADR + MP group were alive. These data indicate that MP provides some protection from Adriamycin-induced cardiotoxicity in rats.
阿霉素（ADR）是一种有效的抗肿瘤药物，但会引起严重的心脏毒性，需要限制剂量。甲基强的松龙（MP）已被证明可稳定细胞膜，并且在缺血性心脏模型中可保护线粒体、溶酶体和肌膜。本研究的目的是确定MP是否能预防大鼠阿霉素诱导的心脏毒性。28只正常雄性Wistar大鼠被分为两组，每组14只。一组每周静脉注射ADR 2mg/kg，共3周，随后每周皮下注射2mg/kg。另一组接受相同剂量的ADR，但在ADR注射前3小时、注射时和注射后3小时还皮下注射MP 20mg/kg。治疗第10周后，每组处死7只大鼠。尸检时，ADR组7/7（100%）的大鼠有明显腹水和胸腔积液，而ADR+MP组0/7出现此并发症（P<0.01）。心脏显微镜检查显示，ADR组7/7（100%）的大鼠有液泡形成、肌肉质量丧失、心肌细胞变细或炎症改变，ADR+MP组为2/7（28%）（P<0.05）。在留作监测存活情况的大鼠中，治疗开始后11周时，ADR组4/7（57%）存活，ADR+MP组7/7（100%）存活。这些数据表明，MP对大鼠阿霉素诱导的心脏毒性有一定的保护作用。
