X射线联合含碲模拟酶抗乳腺癌作用的研究

发布时间：2018-07-27 21:24

【摘要】：活性氧(Reactive oxygen species,ROS)平衡的变化,的在体内会导致例如糖尿病、白内障、心血管疾病、阿尔兹海默症等多种疾病。谷胱甘肽过氧化物酶(GPx)是一种含硒蛋白质,它是一种能够清除体内的过氧化物,在生物体内具有重要的抗氧化作用的酶,具有维持机体内活性氧(ROS)代谢平衡的作用。人们已经对GPx的结构及硒的生物学作用等方面有了全面了解,但由于该酶在不稳定,自然来源有限,分子量相对较大,在人体内容易产生免疫反应等缺点,这些缺点极大地限制了此酶的开发和应用。因此,越来越受的研究人员将重要集中于对这种酶进行人工模拟,开发治疗上述疾病的药物的重视。在本研究中,我们合成了一种十分优秀的GPx模拟物—2-双碲桥联-β-环糊精(2-Te CD),其具有较高的GPx活力。我们对2-Te CD进行了20L级别的放大实验并获得了相关参数,所获得的2-Te CD产率1.58g/L,活力达31.2U/μmol。我们将其作为一种放射性增敏剂来研究,并且用不大于30μM的2-Te CD处理PBMC细胞48h后,来源于三个自愿者的PBMC细胞的存活率分别为94.52、93.76和93.47%,表明该浓度的2-Te CD对正常PBMC细胞的毒性极低。同时放大实验获得的2-Te CD可有效抵抗X-ray致PBMC细胞中DNA裂解率、脂质过氧化水平、ROS含量等指标的变化。在X-ray照射和2-Te CD联合X-ray照射对细胞模型和动物模型的抗癌效果实验中均显示联合应用可以显著抑制MCF-7细胞的体外和体内肿瘤的生长。通过基因水平的分析,我们发现2-Te CD联合X-ray照射导致MCF-7细胞凋亡机制是降低细胞内Bcl-2的表达,提高细胞内Bax的表达。综合我们的实验结果可以看出,X射线联合2-Te CD在抗乳腺癌方面具有重要的应用价值。
[Abstract]:Changes in Ros balance in the body can lead to diseases such as diabetes, cataracts, cardiovascular disease, and Alzheimer's disease. Glutathione peroxidase (GPx) is a kind of protein containing selenium. It is a kind of enzyme which can scavenge the peroxides in vivo and has important antioxidant effect in organism. It can maintain the metabolic balance of reactive oxygen species (ROS) in organism. The structure of GPx and the biological function of selenium have been fully understood. However, because of its instability, limited natural sources, relatively large molecular weight and so on, it is easy to produce immune reaction in human body. These shortcomings greatly limit the development and application of this enzyme. As a result, researchers are increasingly focusing on artificial simulation of the enzyme and the development of drugs to treat the disease. In this study, we synthesized a very excellent GPx mimic, -2-bistellurium bridged 尾 -cyclodextrin (2-Te CD), which has high GPx activity. We have carried out a 20L scale amplification experiment on 2-Te CD and obtained the relevant parameters. The yield of 2-Te CD is 1.58 g / L, and the activity is up to 31.2U/ 渭 mol 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1). We studied it as a radiosensitizer and treated PBMC cells with 2-Te CD not more than 30 渭 M for 48 h. The survival rates of PBMC cells from three volunteers were 94.52 ~ 93.76 and 93.47, respectively, indicating that the toxicity of 2-Te CD to normal PBMC cells was very low. At the same time, 2-Te CD obtained by amplification could effectively resist the changes of DNA cleavage rate, lipid peroxidation level and Ros content in PBMC cells induced by X-ray. In the experiments of anticancer effects of X-ray irradiation and 2-Te CD combined with X-ray irradiation on cell model and animal model, it was shown that combined application could significantly inhibit the growth of MCF-7 cells in vitro and in vivo. Through gene level analysis, we found that 2-Te CD combined with X-ray irradiation induced apoptosis of MCF-7 cells by decreasing the expression of Bcl-2 and increasing the expression of Bax. Our experimental results show that X-ray combined with 2-Te CD has important application value in anti-breast cancer.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R73-36

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