论文部分内容阅读
目的：研究阿霉素（Ｆ－ＡＤＭ）和脂质体阿霉素（Ｌ－ＡＤＭ）对ＮＩＨ小鼠的心脏毒性。方法：采用卵磷脂、磷脂酸和胆固醇制备多层脂质体。实验动物分为阿霉素组和脂质体阿霉素组。其中１ｍｇ·ｋｇ－１对应剂量组观察药物分布；７．５、１５和２０ｍｇ·ｋｇ－１对应剂量组观察药物毒性。结果：用药后４和２４ｈ心肌内药物浓度分别为：阿霉素组８．６１、４．１１μｇ·ｇ－１，脂质体阿霉素组２．５３、０．９８μｇ·ｇ－１。阿霉素１５ｍｇ·ｋｇ－１组５例动物中Ⅲ级以上心肌损害４例，而脂质体阿霉素组无Ⅲ级以上损害。且心、肝、肾病理损害明显减轻。结论：含负电荷磷脂的脂质体载药后可明显减轻阿霉素对心肌的毒性损害。
AIM: To investigate the cardiotoxicity of doxorubicin (F-ADM) and liposomal doxorubicin (L-ADM) to NIH mice. Methods: Multilamellar liposomes were prepared using lecithin, phosphatidic acid and cholesterol. Experimental animals were divided into doxorubicin group and liposomal doxorubicin group. Among them, the dose distribution of 1 mg · kg-1 was observed drug distribution; and the corresponding dose groups of 7.5, 15 and 20 mg · kg-1 were observed drug toxicity. RESULTS: The myocardial drug concentrations at 4 and 24 h after treatment were 8.61 and 4.11 μg · g -1 for doxorubicin and 2.53 and 0.98 μg · g -1 for doxorubicin. Adriamycin 15mg · kg-1 group of 5 animals in grade Ⅲ or more myocardial damage in 4 cases, while the liposomal doxorubicin group Ⅲ grade or more damage. And heart, liver and kidney pathological lesions significantly reduced. Conclusion: The liposomes containing negatively charged phospholipids can obviously reduce the toxic damage of doxorubicin to myocardium.