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鎘毒性干預(yù)治療藥物的初步篩選研究

發(fā)布時(shí)間:2018-06-25 01:12

  本文選題: + 鎘毒性。 參考:《西南交通大學(xué)》2017年碩士論文


【摘要】:鎘污染已經(jīng)成為一個(gè)嚴(yán)重危害人類健康的全球性環(huán)境問(wèn)題,由于鎘廣泛應(yīng)用于電鍍、化工、電子和核工業(yè)等領(lǐng)域,其生物半衰期長(zhǎng)達(dá)10~40年,鎘進(jìn)入機(jī)體后可通過(guò)多種復(fù)雜的途徑對(duì)器官和組織產(chǎn)生損害,但其詳細(xì)毒性作用機(jī)制尚不清楚,已知鎘對(duì)機(jī)體的損傷主要為骨骼損傷、腎損害、生殖毒性和誘導(dǎo)癌癥等。本論文首先以釀酒酵母為模型,研究了 10、20、40、80和160 μM鎘濃度對(duì)釀酒酵母生長(zhǎng)、生長(zhǎng)活力、培養(yǎng)液活菌數(shù)、胞內(nèi)活性氧和谷胱甘肽影響,結(jié)果顯示,濃度高于20μ的鎘對(duì)釀酒酵母生長(zhǎng)抑制明顯,在160 μM鎘濃度下釀酒酵母生長(zhǎng)停滯,釀酒酵母在不同濃度鎘培養(yǎng)條件下,生長(zhǎng)活力和培養(yǎng)液活菌數(shù)隨著鎘濃度的升高而降低,在160 μ高濃度鎘下,釀酒酵母活力低于空白組的20%,培養(yǎng)液活菌數(shù)低于空白組的10%,胞內(nèi)活性氧和谷胱甘肽隨著鎘濃度的升高而升高,在160 μ高濃度鎘下,釀酒酵母胞內(nèi)活性氧和谷胱甘肽高于空白組的2倍。然后以釀酒酵母為模型,通過(guò)單因素實(shí)驗(yàn)和正交實(shí)驗(yàn),以釀酒酵母生長(zhǎng)活力、培養(yǎng)液活菌數(shù)、胞內(nèi)活性氧和谷胱甘肽為指標(biāo),研究了 Zn2+、Fe2+、Mg2+、Ca2+、Se4+、維生素C和半胱氨酸對(duì)鎘毒性干預(yù)治療作用,結(jié)果顯示:加入最適7種物質(zhì)能基本恢復(fù)10和20μM兩種低濃度鎘對(duì)釀酒酵母的影響,在40和80 μM兩種高濃度鎘下,加入7種物質(zhì)能減輕鎘對(duì)釀酒酵母的的影響,但不能達(dá)到恢復(fù)的效果。為了驗(yàn)證酵母模型所篩選微量元素對(duì)鎘毒性干預(yù)治療作用,以及本研究小組前期轉(zhuǎn)錄組測(cè)序分析結(jié)果,在前面實(shí)驗(yàn)的基礎(chǔ)上,通過(guò)小鼠實(shí)驗(yàn)研究了混合物質(zhì)對(duì)低濃度鎘動(dòng)物毒性的預(yù)防和治療作用,所選混合物除釀酒酵母實(shí)驗(yàn)中確定的Zn2+、Fe2+、Mg2+、Ca2+、Se4+、維生素C和半胱氨酸等7種物質(zhì)外還添加了維生素E、維生素B1、維生素B6、血紅素和姜黃素這5種在動(dòng)物體內(nèi)具有抗氧化作用的物質(zhì),小鼠實(shí)驗(yàn)結(jié)果顯示,所選混合物能顯著降低鎘在小鼠腎臟和肝臟中的積蓄,鎘處理組小鼠腎臟和肝臟中鎘含量分別達(dá)到4.77和2.09 μg/g。四組給藥組小鼠腎臟和肝臟中鎘含量低于鎘處理組的50%,所選混合物能恢復(fù)小鼠腎臟和肝臟中過(guò)氧化氫酶、超氧化物歧化酶、谷胱甘肽過(guò)氧化物酶的含量,最后組織切片觀察結(jié)果顯示,所選混合物能減輕鎘對(duì)腎臟和肝臟的毒性作用。慢性鎘中毒是由于鎘在體內(nèi)長(zhǎng)期蓄積而引起的中毒反應(yīng),對(duì)于慢性鎘中毒,目前還沒(méi)有特別有效的解毒方法,而且鎘的毒性是多方面的,單一元素或化合物不能起到完全拮抗鎘毒性的作用,所以在鎘接觸的過(guò)程中,盡早給予有效治療鎘毒性的元素和化學(xué)物的混合物,就能很大程度上防治鎘對(duì)組織器官的毒害。
[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.
【學(xué)位授予單位】:西南交通大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R595

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