阿霉素前体脂质体对大鼠心肝毒性及对实验性肿瘤的作用

The effect of doxorubicin proliposome on toxicity of liver and heart in rats and experimental tumour

目的：研究阿霉素前体脂质体［ｄｏｘｏｒｕｂｉｃｉｎ（ＤＲ），ｐｒｏｌｉｐｏｓｏｍｅ（ＰＬ），ＤＲＰＬ］对大鼠心肝毒性及对荷瘤小鼠的抗肿瘤活性。方法：以酶活性变化为指标，结合病理组织学检查，观察药物对大鼠的心肝毒性及荷瘤小鼠的生命延长率和药物的抗肿瘤活性。实验动物分为ＤＲＰＬ组和ＤＲ组，其中２．００，１４０，０９８ｍｇ·ｋｇ１对应剂量观察药物对大鼠的毒性；４，２，１ｍｇ·ｋｇ１对应剂量观察药物的抗肿瘤活性。结果：与ＤＲＰＬ相比，ＤＲ可明显增加大鼠血清ＬＤＨ、ＣＫ、ＧＰＴ及ＧＯＴ的活性，ＤＲＰＬ对大鼠心肌细胞的损伤明显小于ＤＲ。相同剂量间相比ＤＲＰＬ延长腹水型小鼠移植瘤ＥＡＣ、Ｈｅｐｓ的存活天数明显高于ＤＲ。结论：ＤＲＰＬ对大鼠心肝毒性明显小于相同剂量的ＤＲ，ＤＲＰＬ不但保持了ＤＲ的抗肿瘤活性，而且有明显增效作用。

AIM:To study the cardiac and heratic toxicities and the antitumor activity of doxorubicin(DR) proliposome(PL).METHODS:The activity of enzymes and the histopathological lesions of the tissues were observed to study the toxicities of DRPL and DR, while the survival rate of mice with tumor was recorded to evaluate their antitumor activity. The animals were devided into DRPL or DR groups. The toxicities and the antitumor activity of them were compared at the doses of 2.00, 1.40, 0.98 mg·kg 1 and 4, 2, 1 mg·kg 1 ,respectively.RESULTS:Compared with DRPL, DR significantly increased the activities of LDH,CK,GPT and GOT in serum of rats. DRPL significantly reduced the lesions in heart. With the same dose, DRPL could prolong the survival time of mice with EAC,Heps of ascitic more significantly than DR. CONCLUSION:The cardiac and hepatic toxicities of DRPL were much less serious than those of DR. DRPL not only remained but also significantly strengthened the antitumor activity of DR.