【作者】 刘培民；

【导师】 焦中华；

【作者基本信息】 山东中医药大学 ， 中医内科学， 2003， 博士

【摘要】 本文以动物移植瘤H22肝癌、S180肉瘤为模型，观察中药漏芦醇抽提剂（RHU）不同浓度以及和常见化疗药顺铂、环磷酰胺合用或对比运用对荷瘤动物的抑瘤、增效增敏、增强机体免疫力、延长生存期作用的疗效。检测了不同用药组小鼠体重变化、瘤重、肺体比、脾体比、肝体比、胸腺体比。以人乳腺癌MCF-7敏感株和耐药株MCF-7/ADR为研究对象，分别采用细胞毒试验（MTT法）、流式细胞仪（FCM）和倒置相差显微镜，检测不同用药组体外培养细胞凋亡、BcL-2、端粒酶、P-gp（P170蛋白）等的变化与表达情况。结果显示：RHU抽提剂具有一定的抑瘤作用且有着明显的量效关系；保护机体的免疫力，增加体重，明显延长实验荷瘤动物的生存时间。与西药配合使用，可发挥明显的增效、增敏、减毒作用；可显著下调MDR/P-gp、端粒酶、BcL-2基因表达，而且呈现剂量-疗效关系。因而具逆转耐药和诱导凋亡的作用。 其作用机理为：1．RHU作用于肿瘤细胞G₂/M期，阻滞肿瘤细胞有丝分裂；2．RHU能显著下调肿瘤细胞端粒酶的表达，可诱导肿瘤细胞凋亡；3．RHU影响肿瘤细胞基因表达，能下调促癌生长基因bcl-2表达；4．RHU能显著抑制肿瘤细胞耐药基因MDR/P-gp的表达，抑制耐药细胞膜转运活性，减少耐药细胞对化疗药物的外排，提高细胞内化疗药物浓度，增强对癌细胞的杀伤力，从而逆转肿瘤细胞的耐药性；5．RHU具有有效抗恶病质作用，保护机体的免疫力，增加体重，明显延长实验荷瘤动物的生存时间。以上研究工作可为进一步开发应用清热解毒药漏芦应用于抑瘤，逆转耐药、诱导肿瘤细胞凋亡方面提供重要的参考依据。更多还原

【Abstract】 This paper with animal transplant tumour H22 liver cancer and S180 sarcoma is model, observe the Rhaponticum uniflorum(L.) DC. Chinese medicine mellow wine take out to mention dose (RHU) different density as well as with common melt Liao medicine obey platinum and ring Lin Xian amine suit use or contrast utilize for lotus tumour animal restrain tumour and synergism increase quick , strengthen organism immunity force , prolong the curative effect of survival issue role. Detection not organizes little mouse weight change and tumour weight together with medicine , lung body than , spleen body than , liver body than , chest gland body than. With the person MCF-7 sensitive of breast cancer with endure medicine MCF-7/ADR is research object, difference is tested with cell poison ( MTT law ) , flow cytometry (FCM) with place upside down to differ microscope, detection not withers together with medicine group body outside training cell to die , the change of BcL-2, end grain enzyme and the etc. of P-gp ( P170 proteide ) with express condition. Show as a result: RHU take out to mention dose have certain restrain tumour role have obvious quantity just effect relation; The immunity force of protective organism increases weight , is obvious to prolong the survival time of experiment lotus tumour animal. With the coordination of Western medicine use, can develop obvious synergism , increase quick , reduce poisonous role; Can express apparently under tune MDR/P-gp, telomerase and BcL-2 gene , also present dosage-the relation of curative effect. Thus worse turning endures medicineand guides to wither, is deceased to take affect. Mechanism is its role:1. RHU role in the tumor cell, issue of G2/M, retardance tumor cell has silk to split;2. RHU can hold grain enzyme apparently under tune tumor cell express , it is deceased to guide tumor cell to wither;3. RHU influence tumor cell gene express , can promote cancer growth gene bcl-2 under tune to express;4. RHU can restrain tumor cell apparently endure medicine gene MDR/P-gp express , it is active to restrain to endure medicine cell membrane transfer, decrease to endure medicine cell for melt Liao the outside row of medicine, raise cell melt Liao medicine density, strengthen for cancer cell kill and wound force, so worsen tumor cell endure property of medicine;5. RHU have fight bad ill quality role efficiently, the immunity force of protective organism increases weight , is obvious to prolong the survival time of experiment lotus tumour animal.Above research work can settle heat for further development application detoxify medicine leakage Lu application in restrain tumour, worse turning endures medicine , guide tumor cell wither deceased aspect offer important reference basis.更多还原