【作者】 黄林；

【导师】 张阳德；

【作者基本信息】 中南大学 ， 外科学， 2004， 硕士

【摘要】 目的：半乳糖化白蛋白磁性阿霉素纳米粒治疗大鼠肝脏移植性恶性肿瘤对肿瘤细胞调亡bcl-2及bax蛋白表达的影响。 方法：SD大鼠肝脏移植性恶性肿瘤模型的建立，接种Walker-256腹水型肝癌大鼠的腹水于SD大鼠右后腿腹腹股沟皮下。形成实体瘤后，取实体瘤之条块置入受植鼠左肝外叶。取荷瘤大鼠100只，随机分成注射半乳糖化白蛋白磁性阿霉素纳米粒组(肿瘤区加磁场)，相当于0.5mg/kg阿霉素；半乳糖化白蛋白磁性阿霉素纳米粒组(肿瘤区不加磁场)，相当于0.5mg/kg阿霉素；阿霉素白蛋白磁性纳米粒组，相当于0.5mg/kg阿霉素(肿瘤区加磁场)；注射游离阿霉素组，相当于0.5mg/kg阿霉素；注射生理盐水组。于移植肿瘤术后7天开始，从尾静脉给药，每天一次，连续7天。荷瘤大鼠生存超过1周者，记录生存天数，生存满6w则处死，取肿瘤作组织学切片检查。观察瘤体的大小，湿重，采用SABC法进行免疫组化染色观察bcl-2及bax蛋白的表达。 结果：注射半乳糖化白蛋白磁性阿霉素纳米粒组(肿瘤区加磁场)组、注射半乳糖化白蛋白磁性阿霉素纳米粒组(肿瘤区不加磁场)、ADM组和NS组(肿瘤区加磁场)在存活率、肿瘤体积与湿重的差异有显著性(P＜0.01)。注射半乳糖化白蛋白磁性阿霉素纳米粒(肿瘤区加磁场)组免疫组化显示bcl-2蛋白表达阳性率23.53％低于ADM组54.55％及NS组71.43％(p＜0.01)，bax蛋白表达阳性率88.24％高于ADM组45 .45%及NS组28.57%。 结论:半乳糖化白蛋白磁性阿霉素纳米粒组在适当外加磁场的作用一「，能够降低bcl一2蛋白表达，增加bax蛋白表达，促进移植肝癌肿瘤细胞凋亡。同时bd一2山ax可作为判断肝癌疗效、预后的有效指标。更多还原

【Abstract】 Objective: To evaluate the effect of galactosed magnetic albumin nanoparticle containing adriamycin on expression of bcl-2 and bax protein in transplanted malignant liver tumor of ratsMethods : The male weaning SD rats were inoculated and transgenerated from the celiar transplantation tumor rats (W256-2k) by intraperitoneal injection of abdominal fluid of tumor cells, another weaning SD rats were prepared for the models of solid tumor . The solid tumors were cut to pieces of 0.5mm X 2mm, which were implanted into the liver of the adult male SD rats, So the transplantated malignant liver tumor models in SD rats were established. 100 samples were divided into 5 groups randomly, the tumor experiment group and the tumor control group on the basis of completely random principle after being fed with 6 weeks on routine, and observe the survival rate of rats, then to measure volume and wet weighty of the body of sarcoma .In the last HE and Immunohistochemical double staining technique(SABC) were used to detect the expression of the twogenes.Results: In thr period of the experiment ,it was found that SD rats survival rate(85%) was increased , sarcoma volume(1.17+0.10cm3) and wet weighty(0.12 + 0.01g) were significantly decreased whencompared with the tumor control groups(p<0.01).The pathology examination showed that the number of apoptosis were significantly increased. The positive expression rate(23.53%) of bcl-2 protein was decreased , the positive expression rate(88.24%) of bax was contrary bcl-2 gene. There was significant difference between the experiment group and the tumor control groups(p<0.01).Conclusion: galactosed magnetic albumin nanoparticle containing adriamycin can decrease the expression of bcl-2 gene , increase the expression of bax gene and decrease the ratio of bcl-2/ bax. It shows achieving antitumor effect by inducing apoptosis of SD rat implantation sarcoma cells. Galactosed magnetic albumin nanoparticle containing adriamycin will show potentiation of the antitumor effect as a new clinical means . bcl-2 and bax gene are very useful proof for clinical diagnosis,prognosis and therapy of hepatic carcinoma.更多还原