基于兔VX2原位移植肺癌模型评价多西他赛脂质体疗效和安全性

发布时间：2018-02-02 21:51

本文关键词： 多西他赛脂质体原位移植肺癌模型药效学　出处：《第三军医大学学报》2017年14期 　论文类型：期刊论文

【摘要】：目的评价多西他赛脂质体(DTX-LP)的远期疗效和不良反应。方法建立兔VX2原位移植肺癌模型,分别静脉给予荷瘤兔空白脂质体(BLA-LP)、多西他赛注射剂(DTX-IN,2.7 mg/kg)、DTX-LP高剂量(0.9 mg/kg)、DTX-LP中剂量(0.3 mg/kg)以及DTX-LP低剂量(0.1 mg/kg)治疗4周期,记录兔生存时间并作生存分析,考察兔存活期间体质量及白细胞计数变化率,食欲减退、腹泻、肠道出血发生率,实验兔死亡后作大体解剖,评估主要脏器的组织病理损害程度。结果 BLA-LP组,DTXIN组,DTX-LP高、中、低剂量组兔的中位生存时间分别为28、35、49、34、32 d。生存曲线经Log-Rank检验,DTX-LP高剂量组分别与BLA-LP组、DTX-IN组比较,差异有统计学意义(P=0.001,P=0.005)。上述各治疗组兔的平均体质量变化率分别为(-23.03±7.99)%、(-11.25±9.67)%、(-1.48±6.36)%、(-2.08±14.39)%和(-17.27±18.41)%;白细胞计数累积变化率分别为(-3.53±18.17)%、(-52.78±12.50)%、(-16.56±10.21)%、(-22.19±10.70)%和(-15.37±14.14)%。DTX-IN组和DTX-LP高剂量组食欲减退的发生率分别为83.3%和50.0%;BLA-LP组、DTX-IN组及DTX-LP高、中、低剂量组腹泻发生率分别为16.7%、66.7%、33.3%、16.7%、16.7%;DTX-IN组肠道出血发生率83.3%。病理检查结果显示DTX-LP高剂量组的心、肝、脾、肺、肾组织无明显异常,DTX-IN组上述脏器均有不同程度的病理损害。结论 DTX-LP高剂量组明显延长VX2肺癌兔中位生存期,且不良反应轻微。
[Abstract]:Objective to evaluate the long-term efficacy and adverse reactions of docetaxel liposome DTX-LP.Methods VX2 orthotopic transplantation of lung cancer model was established in rabbits, and BLA-LP was given intravenously to the tumor-bearing rabbit with blank liposome (BLA-LP). The high dose of DTX-LP was 0.9 mg / kg of DTX-LP (2. 7 mg 路kg ~ (-1) 路kg ~ (-1)). The median dose of DTX-LP (0.3 mg / kg) and the low dose of DTX-LP (0.1 mg / kg) were treated for 4 cycles. The survival time of rabbits was recorded and survival analysis was made. The changes of body mass and white blood cell count, anorexia, diarrhea and intestinal hemorrhage were investigated during the survival period of rabbits. The experimental rabbits were dissected after death. Results the median survival time of rabbits in BLA-LP group with high DTX-LP, medium dose and low dose was 280.35%. The survival curve of DTX-LP group was compared with that of BLA-LP group and DTX-IN group by Log-Rank test. The difference was statistically significant (P < 0.001). The average body weight change rate of the above treatment groups was -23.03 卤7.99%. 2.08 卤14.39% and 17.27 卤18.41%; The cumulative change rates of white blood cell count were -3.53 卤18.17% and 52.78 卤12.50%, respectively. -22.19 卤10.70% and 15.37 卤14.14). The incidence of appetite loss in DTX-IN group and DTX-LP high dose group was 83.3% and 50.0 respectively. In BLA-LP group, the incidence of diarrhea in DTX-IN group and DTX-LP group was higher than that in low dose group, and the incidence of diarrhea was 16.7%, 66.7% and 33.3% respectively. The incidence of intestinal hemorrhage in DTX-IN group was 83.3%. Pathological examination showed that the heart, liver, spleen, lung and kidney tissues in the high dose group of DTX-LP were not abnormal. Conclusion the median survival time of rabbits with VX2 lung cancer was significantly prolonged in the high dose group of DTX-LP, and the adverse reaction was mild.
【作者单位】：重庆医科大学附属第一医院药学部;重庆医科大学附属第一医院口腔颌面外科;重庆医科大学药学院药物化学与生物材料研究室;
【基金】：国家自然科学基金面上项目(81172097) 重庆市自然科学基金重点项目(CSTC2013jjB0010)~~
【分类号】：R-332;R965
【正文快照】： 附属第一医院口腔颌面外科2,药学院药物化学与生物材料研究室3)多西他赛(docetaxel,DTX)通过与游离的微管蛋白结合,促进微管蛋白装配并抑制微管解聚,干扰细胞有丝分裂和分裂间期的微管网络而起到抗肿瘤作用,临床上广泛用于非小细胞肺癌等多种实体瘤的单药或联合化疗[1-3]。目

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