Rudolph R, Woodward M, Hurn I
Cancer Res. 1979 Sep;39(9):3689-93.
Skin necrosis was produced in 24 male Fischer 344 rats by intradermal injection of 0.5 ml of doxorubicin (Adriamycin) at a concentration of 2 mg/ml. The resulting wounds healed slowly over 6 to 7 weeks with the reduced contraction rate paralleling the prolonged morbidity of doxorubicin ulcers in humans. Electron microscopy showed bizarre rough endoplasmic reticulum, double-walled vacuoles, and swollen mitochondria from 1 through 12 weeks after injury. Myofibroblasts with 60- to 80-A microfilaments with electron-dense bodies, intercellular connections, and prominent microtubules were seen from 4 through 12 weeks after injury. Although the appearance of myofibroblasts was delayed, their structure was normal. The delayed contraction of doxorubicin-induced skin ulcers thus appears due to persistent nonspecific cellular damage at the nuclear level rather than to specific derangement of myofibroblast function.
通过皮内注射0.5毫升浓度为2毫克/毫升的阿霉素（多柔比星），在24只雄性Fischer 344大鼠身上造成皮肤坏死。由此产生的伤口在6至7周内愈合缓慢，收缩率降低，这与人类阿霉素溃疡的发病时间延长情况相似。电子显微镜检查显示，受伤后1至12周，出现了奇异的粗面内质网、双壁空泡和肿胀的线粒体。受伤后4至12周，可见含有60至80埃微丝、电子致密体、细胞间连接和突出微管的肌成纤维细胞。虽然肌成纤维细胞的出现有所延迟，但其结构正常。因此，阿霉素诱导的皮肤溃疡收缩延迟似乎是由于核水平上持续的非特异性细胞损伤，而非肌成纤维细胞功能的特异性紊乱。
