本文選題：太空射線 + 高能電粒子��； 參考：《武漢大學(xué)》2014年博士論文

【摘要】：背景 高能量帶電荷(high charge and energy, HZE)的粒子(以下簡(jiǎn)稱高能電粒子)是構(gòu)成宇宙射線的重要組成成分。高能電粒子由于其對(duì)機(jī)體不確定的生物學(xué)效應(yīng),成為阻礙人類進(jìn)行太空探索的主要因素之一。高能電粒子通過(guò)少量射線即能傳遞巨大的能量,這種巨大的能量會(huì)對(duì)受輻射機(jī)體造成復(fù)雜而且難以修復(fù)的損傷。有研究表明高能電粒子輻射在嚙齒類動(dòng)物中會(huì)引起腫瘤性病變。另有研究發(fā)現(xiàn)高能電粒子輻射也會(huì)在嚙齒類動(dòng)物中引起一系列非腫瘤性病變,這類非腫瘤性病變包括認(rèn)知和行為的改變、神經(jīng)炎性病變、骨密度降低、慢性血管性損傷,以及腸道中的持續(xù)性氧化應(yīng)激反應(yīng)。針對(duì)這些輻射造成的腫瘤和非腫瘤性病變,目前還沒(méi)有一個(gè)簡(jiǎn)單明了的解釋。雖然與太空探索任務(wù)相關(guān)的高能電粒子輻射劑量較低,僅為0.3Gy或更少,然而由于缺乏有效的解釋,對(duì)太空探索任務(wù)相關(guān)的輻射劑量可能引起的機(jī)體病變也無(wú)法預(yù)測(cè)。 目的 本研究通過(guò)利用一種小型實(shí)驗(yàn)動(dòng)物—青溕(Oryzias latipes,俗稱稻田魚(yú)),進(jìn)行一個(gè)大規(guī)模、終身觀察的實(shí)驗(yàn)。通過(guò)實(shí)驗(yàn),本研究將觀察高能電粒子輻射引起的機(jī)體內(nèi)持續(xù)終身的生物學(xué)效應(yīng),同時(shí)試圖探索其發(fā)生發(fā)展的可能機(jī)制。 方法 本研究將分化處于22-34階段(stage22-34)的青溕魚(yú)魚(yú)卵接受1GeV/nucleon56Fe粒子的輻射。輻射劑量從0.1Gy到9Gy,按照3倍劑量遞增,共分為5組,分別是0.1Gy、0.3Gy、1Gy、3Gy和9Gy。每個(gè)劑量組含有約250枚魚(yú)卵。同時(shí),本研究也做了相似規(guī)模的伽馬射線輻射組,輻射劑量為0.1Gy到27Gy,共分為6組,分別是0.1Gy、0.3Gy、1Gy、3Gy、9Gy和27Gy。本研究對(duì)兩類輻射組分別設(shè)立了不接受輻射的對(duì)照組,對(duì)照組所有處理方式與輻射組相同。本研究選取接受輻射后250天、400天、500天和600天四個(gè)觀察時(shí)間點(diǎn),對(duì)實(shí)驗(yàn)組和對(duì)照組進(jìn)行生存率、發(fā)育水平、組織形態(tài)學(xué)、線粒體功能和轉(zhuǎn)錄組水平的觀察,并對(duì)實(shí)驗(yàn)結(jié)果進(jìn)行相關(guān)性分析,從而試圖對(duì)高能電粒子輻射的生物學(xué)作用及其機(jī)制進(jìn)行探討和說(shuō)明。 結(jié)果 本研究?jī)H在250天以內(nèi)觀察到最高輻射劑量組內(nèi)青淩的急性死亡。直到輻射后600天,其余劑量組的生存率與對(duì)照組比較并無(wú)顯著差異。輻射組與對(duì)照組之間個(gè)體發(fā)育水平也無(wú)顯著差異。本研究于輻射后250天進(jìn)行第一批標(biāo)本觀察,發(fā)現(xiàn)高輻射劑量組內(nèi),青淩肝臟出現(xiàn)肝臟細(xì)胞脂肪樣變、海綿樣變和氣球樣變。之前研究表明,肝臟細(xì)胞的脂肪樣變、海綿樣變和氣球樣變與青淩的自然老齡化高度相關(guān),這些變化多出現(xiàn)于“老年”青淩體內(nèi)(年齡大于24個(gè)月)。因此,本研究將接受輻射后青淩肝臟出現(xiàn)的上述各種變性定義為老齡化相似組織學(xué)變化。本研究針對(duì)老齡化相似組織學(xué)變化,進(jìn)一步研究了輻射后青淩肝臟內(nèi)的氧化應(yīng)激反應(yīng)。4-羥基—2一壬烯醛(4-hydroxy-2-nonenal,4-HNE)是一種脂質(zhì)過(guò)氧化產(chǎn)物,與機(jī)體內(nèi)的氧化應(yīng)激反應(yīng)高度相關(guān)。本研究發(fā)現(xiàn)4-HNE在接受高能電粒子輻射的青淩肝臟內(nèi)有大量聚積(比對(duì)照組高1.8-5倍),而接受伽馬射線輻射后的青溕肝臟內(nèi)4-HNE的聚積程度僅輕度升高,與對(duì)照組無(wú)顯著性差異。線粒體DNA在自然老齡化過(guò)程中會(huì)顯著減少。本研究發(fā)現(xiàn)線粒體DNA在輻射組與對(duì)照組之間并無(wú)顯著差異,但當(dāng)觀察轉(zhuǎn)錄組基因表達(dá)水平時(shí),本研究發(fā)現(xiàn)線粒體調(diào)節(jié)因子過(guò)氧化物酶體增殖活化受體γ共激活因子-1α(PGC-1α)的mRNA在高能電粒子輻射組中顯著降低,接受PGC-1α調(diào)控的雌激素受體相關(guān)蛋白α(ERRα)和依賴于煙酰胺腺嘌呤二核苷酸的去乙�；窼irtuin-3(Sirt3)的mRNA也都有相應(yīng)降低。細(xì)胞周期蛋白依賴性激酶抑制劑1A(CDKN1A)、前列腺素E合酶(PTGES)、超氧化物歧化酶2(SOD2)和過(guò)氧化氫酶(CAT)也有改變。這些改變?cè)诮邮苜ゑR射線輻射組中均不明顯。 結(jié)論 本研究的觀察結(jié)果支持了一種假設(shè)：在發(fā)育階段接受太空探索任務(wù)相關(guān)劑量的高能電粒子輻射會(huì)引起機(jī)體長(zhǎng)期的氧化應(yīng)激反應(yīng)和相關(guān)的改變,這些改變最終導(dǎo)致機(jī)體肝臟提前出現(xiàn)老齡化相似的變化。
[Abstract]:background
High charge and energy (HZE) particles (hereinafter referred to as high-energy particles) constitute an important component of cosmic rays. High energy particles, due to their indeterminate biological effects on the body, become one of the main factors that impede human exploration in space. High energy particles can transmit huge amounts of radiation through a small amount of radiation. Energy, such a huge energy, can cause complex and difficult repair damage to the irradiated body. Studies have shown that high energy particle radiation can cause tumorous lesions in rodents. And other studies have found that high-energy particles radiation also causes a non tumor disease in rodents, such as non tumor lesions. It includes cognitive and behavioral changes, neuritis, bone density reduction, chronic vascular injury, and continuous oxidative stress in the intestine. There is no simple and clear explanation for the tumor and non tumor lesions caused by these radiation. Low, only 0.3Gy or less. However, due to lack of effective explanation, it is impossible to predict the body lesions that may be caused by radiation doses related to space exploration missions.
objective
In this study, a small experimental animal, Oryzias latipes, is used to carry out a large-scale, lifelong observation experiment. Through the experiment, this study will observe the biological effects of continuous lifetime in the body caused by high energy particles radiation, and try to explore the possible mechanism of its development.
Method
In this study, the 22-34 phase (stage22-34) of the blue fish eggs received radiation from the 1GeV/nucleon56Fe particles. The radiation dose increased from 0.1Gy to 9Gy at a dose of 3 times, which were divided into 5 groups, which were 0.1Gy, 0.3Gy, 1Gy, 3Gy and 9Gy. each containing about 250 fish eggs. Meanwhile, this study also made a similar scale of gamma ray radiation. The radiation dose of 0.1Gy to 27Gy was divided into 6 groups, which were 0.1Gy, 0.3Gy, 1Gy, 3Gy, 9Gy and 27Gy., respectively. The control group that did not receive radiation was set up in the two group of radiation groups, and the control group was the same as the radiation group. This study selected four observation time points for 250 days, 400 days, 500 days and 600 days after receiving radiation. In the control group, the survival rate, the level of development, the histomorphology, the mitochondrial function and the level of the transcriptional group were observed, and the correlation analysis of the experimental results was carried out, so as to try to discuss and explain the biological function and mechanism of the high-energy electric particle radiation.
Result
The survival rate of the remaining dose group was not significantly different from that of the control group at the 600 day after radiation, and there was no significant difference in the level of individual development between the radiation group and the control group. The first batch of specimens was observed at 250 days after radiation, and the high spoke was found in this study. In the dose group, the liver cell fatty changes, cavernous changes and balloon like changes in the liver were found in the liver. Previous studies showed that the fatty changes, cavernous changes and balloon like changes in the liver cells were highly related to the natural aging of the green cells. These changes appeared in the "elderly" green bodies (older than 24 months). Therefore, this study will be accepted. .4- hydroxyl 2 one nonylaldehyde (4-hydroxy-2-nonenal, 4-HNE) is a kind of lipid peroxidation product, and oxygen in the body. There was a high degree of correlation between the response of the chemical stress response. This study found that there was a large accumulation of 4-HNE in the liver of young adults receiving high energy radiation (1.8-5 times higher than that of the control group). The accumulation of 4-HNE in the liver of the liver after gamma radiation was only slightly higher, and there was no significant difference between the control group and the control group. The mitochondrial DNA would appear in the natural aging process. The study found that there was no significant difference between the mitochondrial DNA in the radiation group and the control group, but when the gene expression level was observed in the transcriptional group, the mRNA of the mitochondrial regulatory factor peroxisome proliferator activated receptor gamma co activating factor -1 alpha (PGC-1 alpha) decreased significantly in the high-energy particle radiation group and accepted the PGC-1 alpha modulation. The controlled estrogen receptor related protein alpha (ERR alpha) and the mRNA dependent on nicotinamide adenine dinucleotide deacetylase Sirtuin-3 (Sirt3) also decreased correspondingly. Cell cyclin dependent kinase inhibitor 1A (CDKN1A), prostaglandin E synthase (PTGES), superoxide dismutase 2 (SOD2) and catalase (CAT) were also changed. The change was not obvious in gamma radiation group.
conclusion
The results of this study support the assumption that high energy particle radiation from the related doses of space exploration tasks at the stage of development will cause long-term oxidative stress responses and related changes in the body, which eventually lead to a similar ageing of the body's liver in advance.
【學(xué)位授予單位】：武漢大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R85

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 Alexandros Georgakilas;;Detection of clustered DNA lesions: Biological and clinical applications[J];World Journal of Biological Chemistry;2011年07期

2 呂志平;;從媒體角度看市場(chǎng)調(diào)研行業(yè)的新整合[J];廣告大觀(綜合版);2009年02期

，

本文編號(hào)：2035660