本文關(guān)鍵詞： 甲醛 甲醇 聯(lián)合染毒 氧化損傷　出處：《華中師范大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：甲醛(Formaldehyde,FA)是常見(jiàn)的室內(nèi)空氣污染物。室內(nèi)甲醛污染可對(duì)神經(jīng)系統(tǒng)、生殖系統(tǒng)、免疫系統(tǒng)等產(chǎn)生毒性。2014年,美國(guó)國(guó)家研究理事會(huì)明確指出甲醛污染可以導(dǎo)致人類患白血病,但是關(guān)于甲醛致白血病的機(jī)理尚不清楚。為了解甲醛致白血病的機(jī)理,本文從甲醛分子結(jié)構(gòu)出發(fā),以小鼠和離體培養(yǎng)細(xì)胞為研究對(duì)象,探究甲醛毒性機(jī)制,為研究甲醛致白血病的分子機(jī)理提供科學(xué)依據(jù)。本研究首先選用72只SPF級(jí)雄性昆明鼠為受試動(dòng)物,隨機(jī)分為六組,采用灌胃的方式暴露染毒。第一組為生理鹽水對(duì)照組,第二組為甲醛40mg/kg組,第三組為甲醇40 mg/kg,第四組為甲醛10 mg/kg+甲醇30 mg/kg,第五組為甲醛20 mg/kg+甲醇20 mg/kg,第六組為甲醛30 mg/kg+甲醇10 mg/kg,連續(xù)灌胃七天。染毒結(jié)束后,將小鼠麻醉,心臟取血后處死,取小鼠的肝臟,血液,骨髓細(xì)胞,分別檢測(cè)小鼠的氧化應(yīng)激水平(活性氧、丙二醛、谷胱甘肽含量)、甲醛含量、甲醛脫氫酶的相對(duì)表達(dá)量。結(jié)果顯示:與對(duì)照組相比,實(shí)驗(yàn)組的氧化損傷顯著增加;與甲醛10 mg/kg+甲醇30 mg/kg組相比,甲醛30 mg/kg+甲醇10 mg/kg組小鼠肝臟ROS的含量出現(xiàn)顯著下降(p0.05),肝臟MDA存在極顯著下降(p0.01),肝臟GSH存在極顯著升高(p0.01),因此在聯(lián)合染毒組中,隨著甲醛濃度的增加,甲醇濃度的減少,氧化損傷水平有上升的趨勢(shì);實(shí)驗(yàn)用 AHMT(4-amino-3-hydrazine-5-mercaP to-1,2,4-triazole)法測(cè)定甲醛的含量,與空白組相比,血液和骨髓中甲醛含量均無(wú)顯著差異性;采用RT-PCR法,檢測(cè)血液和骨髓中甲醛脫氫酶相對(duì)表達(dá)量,與空白組相比,各染毒組中甲醛脫氫酶的相對(duì)表達(dá)量顯著增加;甲醛40 mg/kg染毒組與甲醇40 mg/kg染毒組甲醛脫氫酶的表達(dá)量有顯著差異(p0.01);與FA30 mg/kg+MeOH 10 mg/kg相比,FA 10 mg/kg+MeOH 30 mg/kg組中甲醛脫氫酶的表達(dá)量極顯著上升(p0.01),聯(lián)合染毒組中甲醛脫氫酶的含量隨著甲醛的增加、甲醇的減少而表現(xiàn)出上升的趨勢(shì)。本研究表明,N_2a細(xì)胞經(jīng)不同濃度的甲醛和甲醇染毒12h后,單獨(dú)染毒組中:低濃度的甲醛/甲醇促進(jìn)細(xì)胞的生長(zhǎng),高濃度的甲醛/甲醇抑制細(xì)胞的生長(zhǎng),細(xì)胞內(nèi)ROS含量與甲醛/甲醇的濃度呈線性相關(guān),與空白組相比,細(xì)胞內(nèi)甲醛和甲醇含量顯著升高,24h修復(fù)后都恢復(fù)到正常水平。聯(lián)合染毒組中:隨著甲醛濃度的增加,細(xì)胞活力下降,ROS含量增加,細(xì)胞內(nèi)甲醛含量增加,修復(fù)后會(huì)到正常水平。與甲醛175μmol/L組相比,甲醇175μmol/L組中FDH相對(duì)表達(dá)量極顯著下降,聯(lián)合染毒組中隨著甲醛濃度的增加,細(xì)胞內(nèi)FDH的表達(dá)量增加。研究表明,甲醛和甲醇的毒性不一致,甲醛毒性機(jī)制可能存在其它方式。
[Abstract]:Formaldehyde is a common indoor air pollutant. Indoor formaldehyde pollution can cause toxicity to nervous system, reproductive system, immune system and so on. In 2014, the National Research Council of the United States clearly pointed out that formaldehyde pollution can lead to human leukemia. However, the mechanism of formaldehyde-induced leukemia is not clear. In order to understand the mechanism of formaldehyde-induced leukemia, this paper studies the mechanism of formaldehyde toxicity from the molecular structure of formaldehyde, taking mice and cultured cells in vitro as research objects. In order to provide scientific basis for studying the molecular mechanism of formaldehyde-induced leukemia, 72 male Kunming mice of SPF grade were randomly divided into six groups. The second group was formaldehyde 40 mg / kg group, the third group was methanol 40 mg / kg, the 4th group was formaldehyde 10 mg/kg methanol 30 mg / kg, 5th group was formaldehyde 20 mg/kg methanol 20 mg / kg, 6th group was formaldehyde 30 mg/kg methanol 10 mg / kg. The liver, blood and bone marrow cells of the mice were taken and the oxidative stress levels (reactive oxygen species, malondialdehyde, glutathione content, formaldehyde content) were measured. The relative expression of formaldehyde dehydrogenase. The results showed that the oxidative damage was significantly increased in the experimental group compared with the control group, and compared with the formaldehyde 10 mg/kg methanol 30 mg/kg group. In the 30 mg/kg methanol 10 mg/kg group, the content of ROS in liver, MDA in liver and GSH in liver were significantly decreased, respectively. Therefore, the concentration of methanol decreased with the increase of formaldehyde concentration in the combined exposure group. The content of formaldehyde in blood and bone marrow was not significantly different from that in blank group, and the relative expression of formaldehyde dehydrogenase in blood and bone marrow was detected by RT-PCR method. Compared with the blank group, the relative expression of formaldehyde dehydrogenase in each exposed group was significantly increased. There was significant difference in the expression of formaldehyde dehydrogenase between the 40 mg/kg group and the methanol 40 mg/kg group, the expression of formaldehyde dehydrogenase in the FA10 mg/kg MeOH 30 mg/kg group was significantly higher than that in the FA30 mg/kg MeOH 10 mg/kg group, and the formaldehyde dehydrogenase level in the combined group was significantly higher than that in the FA30 mg/kg MeOH 10 mg/kg MeOH 30 mg/kg group, while in the combined treatment group the formaldehyde dehydrogenase expression level was significantly higher than that in the FA30 mg/kg MeOH 10 mg/kg group. The content of hydrogenase increases with the increase of formaldehyde, The decrease of methanol showed an increasing trend. This study showed that the cells were exposed to different concentrations of formaldehyde and methanol for 12 h, and the low concentration of formaldehyde / methanol promoted the growth of the cells. High concentration of formaldehyde / methanol inhibited the growth of cells. The content of ROS in the cells was linearly correlated with the concentration of formaldehyde / methanol, compared with the blank group. The contents of formaldehyde and methanol in the cells increased significantly and recovered to normal level after 24 hours of repair. In the combined exposure group, with the increase of formaldehyde concentration, the cell viability decreased and the content of Ros increased, while the content of formaldehyde in the cells increased. Compared with formaldehyde 175 渭 mol/L group, the relative expression of FDH in methanol 175 渭 mol/L group was significantly decreased, while in combined exposure group, the expression of FDH in cells increased with the increase of formaldehyde concentration. The toxicity of formaldehyde is not consistent with that of methanol, and the mechanism of formaldehyde toxicity may exist in other ways.
【學(xué)位授予單位】：華中師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R114

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