汉防己甲素预防裸鼠白血病多药耐药性形成的研究

目的探讨不同浓度汉防己甲素（Tetrandrine，Tet）在不同给药时间对白血病荷瘤小鼠耐药性形成的预防作用。方法建立K562荷瘤小鼠模型，随机分成4组（每组9只）：Tet高（28mg／kg）、中（18mg／kg）、低（5mg／kg）剂量组和对照组（生理盐水）。每组再根据注射Tet和生理盐水的时间不同分为24h、48h、72h三个亚组（每组3只）。观察荷瘤动物的生长情况和肿瘤生长曲线，测定肿瘤生长抑制率，肿瘤生长延迟时间以及生存期的改变。免疫组织化学染色检测各组P．gP、MRPl、LRPl蛋白表达情况。结果汉防己甲素的预防给药可增强阿霉素对小鼠K562实体瘤生长的抑制作用，且随浓度的增加和给药时间的提前，抑制作用增强，肿瘤生长延迟时间增长，生存期延长（P〈0．05）。免疫组织化学染色结果显示：对照组P-gP、MRPl、LRPl蛋白表达分别呈强阳性（P〈0．05），且随Tet浓度的增加和给药时间的提前，实验组P—gP、MRPl、LRPl蛋白的阳性率减弱（P〈0．05）。结论在一定条件下，汉防己甲素具有预防白血病多药耐药形成的作用。

The preventive effects of tetrandrine on the development of multidrug resistance in nude mice

Objective To acquire scientific understanding of the preventive effects of tetrandrine at various degrees of concentration on the development of muhidrug resistance in nude mice given at different times of medication taking. Method K562 xenograft leukemia mode! was first established. In accordance with the times（24hrs, 48hrs and 72hrs） at which the medication was given before the session of chemotherapy, the subjects were then randomly divided into 4 groups, each consisting of 9 mice, namely, group A taking large dose of tetrandrine（20 mg/kg） , group B taking medium-dose of tettrandrine（ 10 mg/kg） , group C taking small-dose of tetrandrine（5 mg/kg） and a control group taking saline. The growth state, growth curve, inhibitary rate of tumor growth, tumor volume growth delay（TGD） time and survival time of mice with tumor were observed. The expression of P-glycoprotein, multidrug resistance protein 1 and lung cancer resistance protein 1 were measured by immunohistochemistry. Findings The prevention injection of tetrandrine ean enhanee the inhibition of doxorubicin（ADM） on the growth of K562 solid tumor. With the concentration increased and earlier injection before the chemotherapy, the inhibition of doxorubicin was also enhanced; the TGD and survival time were extended as well. Similarly, the expression of P-glyeoprotein （p-gp） , multidrug resistance protein l （ MRPI ） and lung cancer resistance protein 1 （ LRPI ） in the control group were strongly positive by immunohistochemistry and the positive rate was weakened. Conclusion Under certain conditions, tetrandrine has the preventive effects on the development of multidrug resistance to leukemia.