多柔比星脂质体注射液与多柔比星注射液大鼠重复给药毒性的比较

目的研究大鼠连续静脉注射给予多柔比星脂质体注射液和多柔比星注射液后对大鼠产生的毒性作用及毒性异同比较。方法 SD大鼠90只,随机分为溶剂对照组、多柔比星脂质体注射液(1 mg/kg)和多柔比星注射液(1 mg/kg)组。各组大鼠每3 d静脉注射1次,连续给药13次,检测其体重、血液生化学、血液学、脏器系数等指标,并进行组织病理学检查。结果多柔比星脂质体注射液1 mg/kg可引起SD大鼠脱毛和溃疡,体重增长明显延缓,PLT、ALT、BUN升高,ALB降低,心脏和肾脏系数增大,胸腺和睾丸系数减小,组织病理学检查结果显示睾丸曲细精管生精上皮脱落,各级生精细胞消失,部分间质水肿;心脏心肌纤维断裂、溶解,横纹及部分细胞核消失;肾脏出现肾小管透明管型等病理组织学病变。与多柔比星脂质体注射液比较,相同剂量下多柔比星注射液亦可引起以上病变,但大鼠脱毛和皮肤溃疡率降低,肾脏毒性和心脏毒性明显增加。结论多柔比星脂质体注射液与普通注射液比较,心脏和肾脏毒性明显减轻,但皮肤毒性明显增加。

Comparison of the repeated dose toxicity of doxorubicin liposome injection and doxorubicin injection in rats

Objective To investigate the repeated dose toxicity of doxorubicin liposome injection and doxorubicin injection in rats. Methods Ninety SD rats (body weight 180-220 g, male:female=1:1) were divided into 3 groups (30 rats in each group), and were administered intravenously with physiological saline, doxorubicin liposome injection (1 mg·kg^-1) and doxorubicin injection (1 mg·kg^-1), respectively, once every three days for thirteen times. The body weight,blood biochemistry, hematology, organ coefficient and histopathology were analyzed for the overall toxicity assessment. Results The rats administered with doxorubicin liposome injection (1 mg/kg) showed hair loss and skin ulcer, significantly reduced growth of body weight, increased levels of urea nitrogen (BUN), alanine aminotransferase (ALT), blood platelet (PLT), and kidney and heart coefficients, decreased thymus and testicular coefficients, myofibrillar rupture and lysis, and partial loss of cell nuclei, hyaline casts in the renal convoluted tubules, interstitial edema and loss of spermatogenic cells in the testicular tubules. Compared with the doxorubicin liposome injection group, similar abnormal changes were also observed in the doxorubicin injection group, but the hair loss and skin ulcer were milder and the heart and kidney toxicities were severer. Conclusions Compared with doxorubicin injection, the doxorubicin liposome injection causes milder heart and kidney toxicity but more serious skin toxicity.