發(fā)布時(shí)間：2018-04-10 20:46

  本文選題：中子 + γ射線　； 參考：《中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院》2006年博士論文

【摘要】：目的：中子輻射對(duì)腸道損傷較γ射線程度重、發(fā)生早、療效差、難恢復(fù)，迄今機(jī)制未明，腸免疫組織參與其損傷修復(fù)過(guò)程，然關(guān)于中子對(duì)腸免疫組織損傷特點(diǎn)及IL-2對(duì)腸上皮損傷及修復(fù)作用及其機(jī)制尚未見(jiàn)報(bào)道。本文研究中子輻射后腸免疫組織病變特點(diǎn)及其對(duì)腸上皮再生調(diào)控作用，為其防治提供新思路。 方法：采用2.5～5.5Gy中子及5.5-12Gyγ射線照射350只BALB／C小鼠和IEC-6細(xì)胞(正常SD大鼠空腸隱窩上皮細(xì)胞)，并用IL-2(25×10~3～1×10~5U／L)及JAK_1阻斷劑A77-1726于照前12h或照后即刻處理細(xì)胞，分別于照后6h，12h，1～5d，7d，14d，21d及28d活殺取材或15min，30min，1h，3h，6h，9h，12h，1～3d收集細(xì)胞，采用光鏡、電鏡、免疫組化、MTT、FACS、免疫印跡等方法對(duì)比研究中子及γ射線照后腸免疫組織損傷、恢復(fù)規(guī)律和IL-2對(duì)IEC-6再生作用及其機(jī)制。 結(jié)果：(1)腸免疫組織病理變化：中子組2.5Gy照后3d內(nèi)，淋巴細(xì)胞發(fā)生凋亡、壞死，5d見(jiàn)再生，14～21d漸恢復(fù)，4.0和5.5Gy照后以壞死多見(jiàn)，未見(jiàn)明顯恢復(fù)；γ射線組5.5Gy照后病變與中子2.5Gy組類(lèi)似，但程度輕、再生早、凋亡多見(jiàn)，12Gy照后損傷程度介于中子4.0～5.5Gy組之間。(2)腸PP內(nèi)T、B細(xì)胞及漿細(xì)胞變化：2.5Gy中子照后5d內(nèi)，進(jìn)行性減少，T／B比例升高，14d后恢復(fù)，其中T及漿細(xì)胞均呈量—效關(guān)系。(3)腸免疫因子變化：2.5Gy中子和5.5Gyγ射線照后5d內(nèi)，IL-2，4及IgA均進(jìn)行性減少，7～10d少量表達(dá)，14d后漸恢復(fù)，IFNγ，TGFβ_3，TNFα和IL-18于照后2d內(nèi)進(jìn)行性減少，3～7d增多，14d后恢復(fù)，均呈量—效關(guān)系。(4)IL-2對(duì)IEC-6作用及IL-2Rβ／JAK_1／STAT_5通路變化：中子4Gy照后3d內(nèi)，，IEC-6增殖活力降低，照后1d凋亡和壞死增多，以壞死為主，γ射線4～12Gy照后1d以凋亡多見(jiàn)；給予IL-2后1～3d，IEC-6增殖活力提高，凋亡減少，且呈量—效關(guān)系，同時(shí)IL-2R表達(dá)增加，JAK_1激酶和轉(zhuǎn)錄因子STAT_5活化增強(qiáng)；IEC-6經(jīng)A77-1726、IL-2與8Gyγ線共處理后24h增殖活力降低，STAT_5活化減弱。 結(jié)論：(1)中子致腸免疫組織損傷重，恢復(fù)慢，損傷期凋亡與壞死并存，4.0和5.5Gy組以壞死為主，而γ射線照射以凋亡為主。(2)內(nèi)源性IgA及腸上皮生長(zhǎng)刺激因子IL-2、IL-4于中子損傷期減少，而生長(zhǎng)抑制及凋亡誘導(dǎo)因子IFNγ，TGFβ，TNFα及IL-18于損傷期增多，進(jìn)一步抑制腸上皮恢復(fù)。(3)4Gy中子照射抑制IEC-6增殖，以壞死損傷為重，而γ射線損傷以凋亡為主，IL-2可促進(jìn)IEC-6增殖，抑其凋亡，活化JAK_1及STAT_5，A77-1726可抑制IL-2的促增殖及活化效應(yīng)，IL-2可通過(guò)活化IL-2Rβ／JAK_1／STAT_5通路而介導(dǎo)其抗輻射效應(yīng)。
[Abstract]:Objective: neutron radiation is more severe than 緯 -ray in intestinal injury, which is earlier, less effective and difficult to recover. So far, the mechanism of neutron radiation is not clear, and intestinal immune tissue participates in the repair process of intestinal injury.However, no reports have been made on the characteristics of neutron damage to intestinal immune tissue and the effects of IL-2 on intestinal epithelium injury and repair.In this paper, we studied the characteristics of intestinal immunopathies after neutron irradiation and their effects on intestinal epithelium regeneration, and provided a new idea for its prevention and treatment.Methods: 350 BALB/C mice and IEC-6 cells (normal SD rats jejunal crypt epithelial cells) were irradiated with 2.5~5.5Gy neutrons and 5.5-12Gy 緯 rays, and treated with IL-2(25 脳 10 ~ (3 +) 1 脳 10 ~ (5) U / L and JAK_1 blockers A77-1726 12 hours before or immediately after irradiation.Results the pathological changes of intestinal immune tissue: apoptosis of lymphocytes occurred within 3 days after irradiation of 2.5Gy in neutron group, 4. 0% and 4. 0% of 5.5Gy were gradually recovered after 5 days of necrosis. The pathological changes of 緯-ray group after 5.5Gy irradiation were similar to those of neutron 2.5Gy group, and the pathological changes of 緯-ray group were similar to those of neutron 2.5Gy group, and the pathological changes of 緯-ray group were similar to those of neutron 2.5Gy group.However, the degree of apoptosis was slight, regeneration was early, and the degree of injury after 12Gy irradiation was between the neutron 4.0~5.5Gy group and the control group (P < 0.05). The changes of TIB cells and plasma cells in PP were observed within 5 days after neutron irradiation with the dose of 2.5 Gy, and the ratio of T- / B gradually decreased and the ratio of T- / B increased after 14 days.There was a dose-effect relationship between T and plasma cells.) the changes of intestinal immune factors (1: 2.5Gy neutrons and 5.5Gy 緯 -rays) within 5 days after irradiation, the levels of IL-2n4 and IgA were gradually decreased after 710 days, and the expression of TGF- 尾 3TNF- 偽 and IL-18 were gradually restored after 710 days of irradiation, and the levels of TGF- 尾 3- TNF- 偽 and IL-18 gradually decreased within 2 days after irradiation and increased after 14 days of irradiation, and the levels of TGF- 尾 3 TNF- 偽 and TGF- 尾 3 TNF- 偽 were increased after 14 days of irradiation.Apoptosis was decreased in a dose-dependent manner. Meanwhile, the expression of IL-2R increased and the activation of JAKS-1 kinase and transcription factor STAT_5 increased. IEC-6 decreased the activity of STAT5 after co-treatment with A77-1726, IL-2 and 8Gy 緯 rays for 24 hours.Conclusion Neutron-induced intestinal immune tissue injury is severe and slow. Necrosis is the main factor in 4.0 and 5.5Gy group, while 緯 -ray irradiation is mainly apoptosis-induced) endogenous IgA and IL-2IL-4 decrease during neutron injury.However, the growth inhibition and apoptosis inducing factor IFN 緯 TGF- 尾 TNF- 偽 and IL-18 increased during the injury period, further inhibited the intestinal epithelium recovery. 3Gy neutron irradiation inhibited the proliferation of IEC-6, and the necrosis injury was the most serious. However, the 緯 -ray injury mainly caused by apoptosis and IL-2 could promote the proliferation and inhibit the apoptosis of IEC-6.Activation of JAK_1 and STAT5A77-1726 can inhibit the proliferation and activation effects of IL-2. IL-2 can mediate the anti-radiation effect by activating the 1 / 1 / STAT5 pathway of IL-2R 尾 / JAKS.
【學(xué)位授予單位】：中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類(lèi)號(hào)】：R363

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