外源性甲醛对小鼠血液中甲醛含量的稳定性及甲醛远距离毒性的研究

发布时间：2018-03-26 04:32

本文选题：甲醛　切入点：AHMT法　出处：《华中师范大学》2013年硕士论文

【摘要】：长久以来,甲醛在工业生产、实验室以及护肤彩妆中得到了广泛应用。同时,甲醛成为室内主要的空气污染物之一。因此,甲醛的一直是环境毒理学家研究领域的热点之一。2004年6月15日,世界卫生组织(WHO)下属的国际癌症研究组织(Group I)基于“甲醛能引起人类鼻咽癌”这一结论,将甲醛列为人类致癌物。纵观国内外,工业生产上甲醛的职业暴露,房屋装修带来的甲醛等有害室内污染物暴露让人类尤其是儿童罹患白血病几率增长快速。2009年,国际癌症研究组织基于大量流行病学调查报告,判定“甲醛能引起白血病”具有“强有力但不充分”的证据。自此甲醛与白血病的相关性研究成为另一大研究热点。有研究显示,大鼠,恒河猴乃至人类在经一定剂量的外源性甲醛暴露后,其血液中内源性甲醛含量与暴露前相比变化甚微。这一有趣的现象值得我们深思。为了探讨外源性甲醛是否能引起小鼠体内血液中内源性甲醛含量,及相应的血液中甲醛脱氢酶是否通过高效表达以维持血液中甲醛含量的稳定；为了研究甲醛的毒性是否来自于化学基团；同时为了厘清“甲醛的远距离毒性机制来自于甲醛自身进入了骨髓等靶器官”和“甲醛并非直接进入靶器官,而是以其他形式引起远距离毒性”。本研究采用5周龄雄性昆明小鼠作为实验对象,分别采用10mg/kg,20mg/kg和40mg/kg的甲醛,甲醇,甲酸及乙醛这四种物质进行为期一周的灌胃染毒。染毒过程中,甲醛各浓度组的小鼠体重在第一和第二天出现显著下降,而空白组和其它染毒组的小鼠体重维持每天增长的正常趋势。染毒结束后,对小鼠血液中甲醛含量进行测定。随着染毒浓度上升,甲醛各染毒组血液甲醛含量变化无显著性,维持在0.3到0.348mg/L之间。然而在甲醇和甲酸的20mg/kg和40mg/kg浓度组,甲醛含量相比空白组出现了显著性。采用实时荧光定量PCR技术检测中浓度下甲醛组、甲醇组、甲酸组和乙醛组的甲醛脱氢酶的表达量分别为10.20,6.41,2.55和1.81。甲醛含量与甲醛脱氢酶表达量的测定结果充分说明：在机体遭受外源性甲醛侵害时,机体内的甲醛脱氢酶经过高效诱导,对清除多余甲醛、维持血液中甲醛含量的稳定起着关键作用。对全血细胞进行计数发现,与空白组相比,各染毒组中血细胞成分均未出现显著性变化,但仅甲醛组的中性粒细胞数目出现下降。肝脏组织和血液组织的ROS水平结果趋势一致。甲醛组中,无论肝脏还是血液中的ROS水平都高于其他染毒组的水平。最后,对小鼠骨髓中的甲醛含量进行了测定。结果显示,各染毒组的甲醛含量基本持平,未发生改变。以上结果显示：外源性甲醛暴露不能显著改变体内甲醛含量,外源性甲醛诱导体内甲醛脱氢酶高效表达,清除造成危害的多余甲醛。但是当外源性甲醛进入机体的时候,甲醛给机体带来的损伤已经存在,无法消除。并且甲醛的毒性并非来自于其化学基团——醛基或者甲基。最后,各染毒物质染毒结束后都无法在骨髓这一靶器官测得甲醛含量的显著性增高或降低,足以说明甲醛分子并非直接进入骨髓而产生毒性,推测其可能与信号分子类似,通过逐级信号放大引发毒性。如若能从信号途径着手研究,对证明甲醛与白血病相关性应可以提供更多有力证据。
[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.

【学位授予单位】：华中师范大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R114

【参考文献】