镉毒性干预治疗药物的初步筛选研究

发布时间：2018-06-25 01:12

  本文选题：镉 + 镉毒性　； 参考：《西南交通大学》2017年硕士论文

【摘要】：镉污染已经成为一个严重危害人类健康的全球性环境问题,由于镉广泛应用于电镀、化工、电子和核工业等领域,其生物半衰期长达10～40年,镉进入机体后可通过多种复杂的途径对器官和组织产生损害,但其详细毒性作用机制尚不清楚,已知镉对机体的损伤主要为骨骼损伤、肾损害、生殖毒性和诱导癌症等。本论文首先以酿酒酵母为模型,研究了 10、20、40、80和160 μM镉浓度对酿酒酵母生长、生长活力、培养液活菌数、胞内活性氧和谷胱甘肽影响,结果显示,浓度高于20μ的镉对酿酒酵母生长抑制明显,在160 μM镉浓度下酿酒酵母生长停滞,酿酒酵母在不同浓度镉培养条件下,生长活力和培养液活菌数随着镉浓度的升高而降低,在160 μ高浓度镉下,酿酒酵母活力低于空白组的20%,培养液活菌数低于空白组的10%,胞内活性氧和谷胱甘肽随着镉浓度的升高而升高,在160 μ高浓度镉下,酿酒酵母胞内活性氧和谷胱甘肽高于空白组的2倍。然后以酿酒酵母为模型,通过单因素实验和正交实验,以酿酒酵母生长活力、培养液活菌数、胞内活性氧和谷胱甘肽为指标,研究了 Zn2+、Fe2+、Mg2+、Ca2+、Se4+、维生素C和半胱氨酸对镉毒性干预治疗作用,结果显示:加入最适7种物质能基本恢复10和20μM两种低浓度镉对酿酒酵母的影响,在40和80 μM两种高浓度镉下,加入7种物质能减轻镉对酿酒酵母的的影响,但不能达到恢复的效果。为了验证酵母模型所筛选微量元素对镉毒性干预治疗作用,以及本研究小组前期转录组测序分析结果,在前面实验的基础上,通过小鼠实验研究了混合物质对低浓度镉动物毒性的预防和治疗作用,所选混合物除酿酒酵母实验中确定的Zn2+、Fe2+、Mg2+、Ca2+、Se4+、维生素C和半胱氨酸等7种物质外还添加了维生素E、维生素B1、维生素B6、血红素和姜黄素这5种在动物体内具有抗氧化作用的物质,小鼠实验结果显示,所选混合物能显著降低镉在小鼠肾脏和肝脏中的积蓄,镉处理组小鼠肾脏和肝脏中镉含量分别达到4.77和2.09 μg/g。四组给药组小鼠肾脏和肝脏中镉含量低于镉处理组的50%,所选混合物能恢复小鼠肾脏和肝脏中过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶的含量,最后组织切片观察结果显示,所选混合物能减轻镉对肾脏和肝脏的毒性作用。慢性镉中毒是由于镉在体内长期蓄积而引起的中毒反应,对于慢性镉中毒,目前还没有特别有效的解毒方法,而且镉的毒性是多方面的,单一元素或化合物不能起到完全拮抗镉毒性的作用,所以在镉接触的过程中,尽早给予有效治疗镉毒性的元素和化学物的混合物,就能很大程度上防治镉对组织器官的毒害。
[Abstract]:Cadmium pollution has become a global environmental problem that seriously endangers human health. Because cadmium is widely used in electroplating, chemical industry, electronics and nuclear industry, its biological half-life lasts for 10 to 40 years. Cadmium can cause damage to organs and tissues through a variety of complex ways, but the detailed mechanism of its toxicity is not clear. It is known that cadmium damage to the body is mainly skeletal damage, kidney damage, reproductive toxicity and cancer induction and so on. In this paper, the effects of cadmium concentrations of 100.20, 4080 and 160 渭 M on the growth, viability, viable bacteria, intracellular reactive oxygen species and glutathione of Saccharomyces cerevisiae were studied by using Saccharomyces cerevisiae as a model. The growth of Saccharomyces cerevisiae was inhibited obviously when cadmium concentration was higher than 20 渭 m, and the growth of Saccharomyces cerevisiae stopped at the concentration of 160 渭 M CD. Under different cadmium concentrations, the growth activity and the number of viable bacteria in culture medium decreased with the increase of cadmium concentration. The activity of Saccharomyces cerevisiae was lower than that of the blank group (20%), the number of viable bacteria in the culture medium was lower than that of the control group (10%), and the intracellular reactive oxygen species (Ros) and glutathione (GSH) increased with the increase of cadmium concentration. Intracellular reactive oxygen species and glutathione in Saccharomyces cerevisiae were 2 times higher than those in the control group. Using Saccharomyces cerevisiae as a model, the growth activity of Saccharomyces cerevisiae, the number of viable bacteria in culture medium, intracellular reactive oxygen species and glutathione were used to study Zn _ 2 Fe _ 2, mg _ 2 and Ca ~ (2 +) (Ca ~ (2 +) se _ (4) by single factor experiment and orthogonal experiment. The effects of vitamin C and cysteine on the toxicity of cadmium were studied. The results showed that the optimal concentration of 7 substances could restore the effects of 10 渭 M and 20 渭 M on Saccharomyces cerevisiae basically, and at 40 渭 M and 80 渭 M, respectively. The effects of cadmium on Saccharomyces cerevisiae were alleviated by adding 7 substances, but the effect of recovery could not be achieved. In order to verify the therapeutic effect of trace elements screened by yeast model on cadmium toxicity and the results of preliminary transcriptome sequencing of the study group, based on the previous experiments, The preventive and therapeutic effects of the mixture on the toxicity of low concentration cadmium in animals were studied in mice. The selected mixture was used to remove Zn _ (2 +) Fe _ (2) O _ (2) mg _ (2) O _ (2) Ca ~ (2 +) (E _ (2) O _ (4), Vitamin C, cysteine and other seven substances were supplemented with vitamin E, vitamin B1, vitamin B6, heme and curcumin, which have antioxidant activity in animals. The concentration of cadmium in kidney and liver of mice treated with cadmium was 4.77 渭 g / g and 2.09 渭 g / g, respectively. The contents of cadmium in kidney and liver of mice in the four groups were lower than those in the cadmium treatment group. The selected mixture could restore the contents of catalase, superoxide dismutase and glutathione peroxidase in kidney and liver of mice. The final histological observation showed that the mixture could reduce the toxicity of cadmium to kidney and liver. Chronic cadmium poisoning is a toxic reaction caused by the accumulation of cadmium in the body for a long time. There is no especially effective detoxification method for chronic cadmium poisoning, and the toxicity of cadmium is various. Single element or compound can not antagonize the toxicity of cadmium completely, so in the process of cadmium exposure, the mixture of elements and chemicals which can effectively treat cadmium toxicity can prevent and cure the toxicity of cadmium on tissues and organs to a great extent.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R595

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