腹腔注射纳米硒抑制小鼠腹腔内癌细胞增殖的研究

发布时间：2018-11-19 07:29

【摘要】：对于哺乳动物来说,硒是必不可少的微量元素,对于维持人体正常生理功能、调节代谢、抗氧化损伤等都有不可替代的作用。硒的生物效应与其化学形式相关,通常,在人们的观念中,零价态的硒是没有生理活性的,而本室用亚硒酸钠与谷胱甘肽反应,利用牛血清白蛋白为分散剂,制作了胶体状红色元素纳米硒,其生物活性不低于其他形式硒,而毒性显著较低。这一发现改变了传统上认为零价硒无生物活性的观念。腹腔内的肿瘤,有胃癌、结肠癌、肝癌、卵巢癌等等,患这些癌症的病人经手术后,易有残留的癌细胞留存在腹腔内,若处理不当,容易发生癌细胞的腹腔种植转移,形成腹水或是转移性肿瘤,由于癌细胞接触面广,位点的多发性,这种转移很难再进行治愈。而硒作为人体必需的微量元素,具有癌症预防的功效。本实验中,我们采用腹腔注射的方式评估了硒对于腹腔内癌细胞增殖的抑制作用。使用具有高度恶性水平的小鼠肝癌H22细胞注射入小鼠腹腔内作为模型,后将纳米硒注射入小鼠腹腔内进行实验。对纳米硒进入腹腔之后在癌细胞以及组织内的浓度分布进行了测定,对硒的效用及安全性也进行了评价。结果显示纳米硒能够有效抑制小鼠腹腔内癌细胞的生长,与纳米硒呈现剂量依赖的效果。对小鼠进行安全性测试结果表明,在纳米硒发挥有效抑癌效果的剂量条件下,纳米硒安全无毒。对腹腔注射纳米硒后小鼠组织内硒含量的测定结果表明,纳米硒主要分布于癌细胞而非正常组织中,并且显示出了至少十倍的浓度分布差异。这种浓度分布的差异可有效杀灭癌细胞,抑制腹腔内的癌细胞增殖,并且降低对机体产生毒性的可能性。纳米硒诱导癌细胞毒性的机制与硒介导的活性氧产生相关,活性氧影响了机体内谷胱甘肽系统和硫氧还蛋白系统行使正常功能,促进了细胞凋亡。我们的结果显示采用腹腔注射的方式对于预防高危人群的癌细胞腹腔内扩散增殖安全有效。
[Abstract]:For mammals, selenium is an essential trace element, which has irreplaceable effects on maintaining normal physiological function, regulating metabolism and antioxidant damage. The biological effect of selenium is related to its chemical form. Generally speaking, zero valence selenium has no physiological activity, whereas sodium selenite reacts with glutathione and bovine serum albumin is used as dispersant. The colloidal red element nano selenium was prepared, and its biological activity was not lower than that of other forms of selenium, but the toxicity was significantly lower. The finding changes the conventional belief that zero-valent selenium is bioactive. Cancer in the abdominal cavity, stomach cancer, colon cancer, liver cancer, ovarian cancer, and so on. After surgery, patients with these cancers are prone to residual cancer cells remaining in the abdominal cavity. If they are not properly handled, the cancer cells are likely to develop intraperitoneal implantation and metastasis. The formation of ascites or metastatic tumors is difficult to cure because of the wide contact and multiple loci of cancer cells. Selenium, as a necessary trace element, has the effect of cancer prevention. In this study, we evaluated the inhibitory effect of selenium on the proliferation of intraperitoneal cancer cells by intraperitoneal injection. H22 cells with high malignant level were injected into the abdominal cavity of mice and then nano-selenium was injected into the abdominal cavity of mice for experiment. The concentration distribution of selenium nanoparticles in cancer cells and tissues was determined after entering the abdominal cavity. The efficacy and safety of selenium were also evaluated. The results showed that nano selenium could effectively inhibit the growth of cancer cells in the abdominal cavity of mice in a dose-dependent manner. The safety test of mice showed that nano-selenium was safe and non-toxic under the dosage of effective inhibition effect of nano-selenium. The determination of selenium content in mice tissues after intraperitoneal injection of nano-selenium showed that nano-selenium mainly distributed in cancer cells but not in normal tissues and showed at least 10-fold difference in concentration distribution. This concentration distribution can effectively kill cancer cells, inhibit the proliferation of cancer cells in the abdominal cavity, and reduce the possibility of toxicity to the body. The mechanism of the toxicity induced by nano-selenium is related to the production of reactive oxygen species mediated by selenium. Reactive oxygen species affect the normal function of glutathione system and thioredoxin system and promote apoptosis. Our results show that intraperitoneal injection is safe and effective in preventing the proliferation of cancer cells in high risk groups.
【学位授予单位】：安徽农业大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R151

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