本文選題：甲醛　切入點：AHMT法　出處：《華中師范大學(xué)》2013年碩士論文

【摘要】：長久以來,甲醛在工業(yè)生產(chǎn)、實驗室以及護(hù)膚彩妝中得到了廣泛應(yīng)用。同時,甲醛成為室內(nèi)主要的空氣污染物之一。因此,甲醛的一直是環(huán)境毒理學(xué)家研究領(lǐng)域的熱點之一。2004年6月15日,世界衛(wèi)生組織(WHO)下屬的國際癌癥研究組織(Group I)基于“甲醛能引起人類鼻咽癌”這一結(jié)論,將甲醛列為人類致癌物�？v觀國內(nèi)外,工業(yè)生產(chǎn)上甲醛的職業(yè)暴露,房屋裝修帶來的甲醛等有害室內(nèi)污染物暴露讓人類尤其是兒童罹患白血病幾率增長快速。2009年,國際癌癥研究組織基于大量流行病學(xué)調(diào)查報告,判定“甲醛能引起白血病”具有“強(qiáng)有力但不充分”的證據(jù)。自此甲醛與白血病的相關(guān)性研究成為另一大研究熱點。 有研究顯示,大鼠,恒河猴乃至人類在經(jīng)一定劑量的外源性甲醛暴露后,其血液中內(nèi)源性甲醛含量與暴露前相比變化甚微。這一有趣的現(xiàn)象值得我們深思。為了探討外源性甲醛是否能引起小鼠體內(nèi)血液中內(nèi)源性甲醛含量,及相應(yīng)的血液中甲醛脫氫酶是否通過高效表達(dá)以維持血液中甲醛含量的穩(wěn)定；為了研究甲醛的毒性是否來自于化學(xué)基團(tuán)；同時為了厘清“甲醛的遠(yuǎn)距離毒性機(jī)制來自于甲醛自身進(jìn)入了骨髓等靶器官”和“甲醛并非直接進(jìn)入靶器官,而是以其他形式引起遠(yuǎn)距離毒性”。本研究采用5周齡雄性昆明小鼠作為實驗對象,分別采用10mg/kg,20mg/kg和40mg/kg的甲醛,甲醇,甲酸及乙醛這四種物質(zhì)進(jìn)行為期一周的灌胃染毒。染毒過程中,甲醛各濃度組的小鼠體重在第一和第二天出現(xiàn)顯著下降,而空白組和其它染毒組的小鼠體重維持每天增長的正常趨勢。染毒結(jié)束后,對小鼠血液中甲醛含量進(jìn)行測定。隨著染毒濃度上升,甲醛各染毒組血液甲醛含量變化無顯著性,維持在0.3到0.348mg/L之間。然而在甲醇和甲酸的20mg/kg和40mg/kg濃度組,甲醛含量相比空白組出現(xiàn)了顯著性。采用實時熒光定量PCR技術(shù)檢測中濃度下甲醛組、甲醇組、甲酸組和乙醛組的甲醛脫氫酶的表達(dá)量分別為10.20,6.41,2.55和1.81。甲醛含量與甲醛脫氫酶表達(dá)量的測定結(jié)果充分說明：在機(jī)體遭受外源性甲醛侵害時,機(jī)體內(nèi)的甲醛脫氫酶經(jīng)過高效誘導(dǎo),對清除多余甲醛、維持血液中甲醛含量的穩(wěn)定起著關(guān)鍵作用。對全血細(xì)胞進(jìn)行計數(shù)發(fā)現(xiàn),與空白組相比,各染毒組中血細(xì)胞成分均未出現(xiàn)顯著性變化,但僅甲醛組的中性粒細(xì)胞數(shù)目出現(xiàn)下降。肝臟組織和血液組織的ROS水平結(jié)果趨勢一致。甲醛組中,無論肝臟還是血液中的ROS水平都高于其他染毒組的水平。最后,對小鼠骨髓中的甲醛含量進(jìn)行了測定。結(jié)果顯示,各染毒組的甲醛含量基本持平,未發(fā)生改變。 以上結(jié)果顯示：外源性甲醛暴露不能顯著改變體內(nèi)甲醛含量,外源性甲醛誘導(dǎo)體內(nèi)甲醛脫氫酶高效表達(dá),清除造成危害的多余甲醛。但是當(dāng)外源性甲醛進(jìn)入機(jī)體的時候,甲醛給機(jī)體帶來的損傷已經(jīng)存在,無法消除。并且甲醛的毒性并非來自于其化學(xué)基團(tuán)——醛基或者甲基。最后,各染毒物質(zhì)染毒結(jié)束后都無法在骨髓這一靶器官測得甲醛含量的顯著性增高或降低,足以說明甲醛分子并非直接進(jìn)入骨髓而產(chǎn)生毒性,推測其可能與信號分子類似,通過逐級信號放大引發(fā)毒性。如若能從信號途徑著手研究,對證明甲醛與白血病相關(guān)性應(yīng)可以提供更多有力證據(jù)。
[Abstract]:For a long time, formaldehyde in industrial production, laboratory and skin care cosmetics has been widely used. At the same time, formaldehyde has become one of the main indoor air pollutants. Therefore, formaldehyde has been the research field of environmental toxicologist is one of the focuses in the.2004 in June 15th, the WHO (WHO) affiliated International Cancer Research (Group I) based on the "formaldehyde can cause human nasopharyngeal carcinoma" this conclusion, formaldehyde is carcinogenic to humans. At home and abroad, the industrial production of formaldehyde occupation exposure, housing decoration brings indoor formaldehyde and other harmful pollutants exposure to human especially children suffering from leukemia risk of the rapid growth of.2009, the organization of international cancer research epidemiological investigation report based on decision "formaldehyde can cause leukemia" with "strong but not sufficient" evidence. Since the relationship between formaldehyde and leukemia has become another A great focus of research.
Studies have shown that rat, monkey and human in Ganges RIver after a certain dose of exogenous formaldehyde exposure, the endogenous formaldehyde content in blood and pre exposure compared to little change. This interesting phenomenon worthy of our consideration. In order to investigate whether exogenous formaldehyde can cause endogenous formaldehyde content of blood in mice, and whether the corresponding formaldehyde the blood through the high expression of dehydrogenase to maintain the formaldehyde content in the blood; in order to investigate whether the toxicity of formaldehyde from chemical groups; at the same time in order to clarify the mechanism of toxicity of formaldehyde from remote formaldehyde itself into the bone marrow organ "and" formaldehyde is not directly into the target organ, but in other forms of remote cause toxicity ". This study used 5 week old male Kunming mice were used as experimental objects, 10mg/kg, formaldehyde, 20mg/kg and 40mg/kg of formic acid and methanol. The four substances acetaldehyde for a week gavage. During the treatment, the body weight of mice formaldehyde concentration group decreased significantly in the first and second days, normal weight control group and other trends in exposure group of mice per day to maintain growth. After the end of the exposure, the formaldehyde content in blood of mice were determined. As the exposure concentration increased, the changes of formaldehyde exposed groups, blood formaldehyde content is not significant, maintained at between 0.3 to 0.348mg/L. However, in 20mg/kg and 40mg/kg concentrations of methanol and formic acid, formaldehyde content compared to the blank group appeared significantly. With the concentration detected by real-time fluorescence quantitative PCR in methanol formaldehyde group, group, expression the amount of formaldehyde and acetaldehyde dehydrogenase acid group group were 10.20,6.41,2.55 and 1.81. content determination results of formaldehyde content and formaldehyde dehydrogenase expression implies that the organism is subjected to exogenous formaldehyde invasion And when the body of the formaldehyde dehydrogenase by high performance induction, to remove excess formaldehyde, plays a key role in maintaining the formaldehyde content in the blood. The blood cells were counted, compared with the control group, there were no significant changes in blood cell components in all groups, but only the number of neutrophils formaldehyde group the level of ROS decreased. The results of liver tissue and blood tissue trend. The formaldehyde group, either liver or blood levels of ROS were higher than that in other groups the level. Finally, the formaldehyde content of bone marrow in mice were determined. The results showed that the formaldehyde content of the infected groups was essentially flat, not changed.
The above results showed that exogenous formaldehyde exposure did not significantly alter the formaldehyde content in vivo, high expression in vivo formaldehyde dehydrogenase induced by exogenous formaldehyde removal caused by excess formaldehyde harm. But when the exogenous formaldehyde into the body, to the body damage caused by formaldehyde already exist, can not eliminate the toxicity of formaldehyde. And not from its chemical aldehyde or methyl group. Finally, the significance of toxigens after exposure to the target organ in the bone marrow measured formaldehyde content increased or decreased, illustrates the formaldehyde molecules are not directly into the bone marrow toxicity, suggesting that it may be similar to signal molecules, leading to toxicity amplification step by step if the signal. From the aspect of signal pathway, to prove the correlation between formaldehyde and leukemia should provide more powerful evidence.

【學(xué)位授予單位】：華中師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R114

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