纳米羟喜树碱对原位肝肿瘤小鼠药效学研究.doc

纳米羟喜树碱研究。羟喜树碱study of Pharmacodynamics of Hydroxycamptothec Nanoparticles Injection on Orthotopic liver tumors in mice WEN Liujing，YAN Zhao(Tianjin Medical University Cancer Hospital, Tianjin 300060，China) ABSTRACT OBJECTIVE: To explore improved nano hydroxycamptothecin treatment of Mouse liver cancer model. METHODS: To record weight changes；observe the growth of implanted tumors and changes of pathological in the state；calculate the rate of tumor inhibition，according to tumor size; test MTT and the mouse tumor cell apoptosis in tumor detection RESULTS:Compared with control group, HCPT injection group and nano-preparation group can inhibit the growth of liver cancer in mice in situ, the inhibition rate of nano-HCPT was higher than the injection group (p0.05); the inhibition rate was 48.76%. MTT Display: the inhibition rate to the tumor cells and liver cells of nano-HCPT were 82.63% and 27.1%, the apoptosis rate of nano-HCPT group was 49.72 ± 7.51%，according to results of flow cytometry markers. CONCLUSION: Compared with injection-type HCPT, The nano-HCPT can stabilize the lactone ring structure and increase the organizational affinity and improve the targeting efficacy，which was a new form of improved reliability. hydroxycamptothecin; nanometer; hepatocarcinoma; pharmacodynamics 羟喜树碱(10-hydroxycamptothecin,HCPT)是将喜树碱（CPT）基本环A环中的1O位-H由-OH取代合成的拓扑异构酶I抑制剂。现阶段主要用于结、直肠癌的化疗、介入治疗肝癌、膀胱癌术后膀胱灌注化疗等，且无交叉耐药。HCPTNaOH溶液形成钠盐。在生理条件下可转化成内酯型，占总药量的10％～20％，血浆浓度低存留时间短（T1/2），并难于通过生物膜进入组织和细胞。利用脂质体技术将HCPT内酯包和成200nm左右的颗粒，使其能在水中混悬并经静脉注射进入血液因此，搞清HCPT对原位肝癌小鼠的药效学研究，就成为纳米HCPT进入临床之前的一项至关重要的研究工作1 材料 1.1动物 选用，雌雄兼用由动物中心提供，1.2仪器注射用羟喜树碱，黄石李时珍药业集团武汉李时珍药业有限公司规格5mg；10-羟喜树碱脂质体，湖北医学院药学院规格1mg；PBS；RNase A；溴化丙啶染色液PI只随机分成组，每组只组；组静脉。给药剂量5mg·kg-1(GR)，GR=(治疗后的V／治疗前的V-1)×100％，计算抑瘤率(%)＝(对照组平均瘤重-治疗组平均瘤重)/对照组平均瘤重×100%四甲基偶氮唑盐法250μg·ml-1HCPT冻干粉针和纳米制剂，24h后，换成MTT培养液，37℃培养4h后移去，加入DMSO，振荡混匀10min后，用96孔Biolisa酶标仪检测570 nm处的吸光度值A，比较肝肿瘤细胞和正常肝细胞增值抑制率，增值抑制率=【（对照组A值-实验组A值）/对照组A值】固定离心去上清，细胞重悬在0.4 mL的PBS中，加10μL 100μg /mL RNase A，37处理