中子及γ射线对肠免疫组织放射损伤效应及IL-2对肠上皮再生调控研究

发布时间：2018-04-10 20:46

本文选题：中子 + γ射线　；参考：《中国人民解放军军事医学科学院》2006年博士论文

【摘要】：目的：中子辐射对肠道损伤较γ射线程度重、发生早、疗效差、难恢复，迄今机制未明，肠免疫组织参与其损伤修复过程，然关于中子对肠免疫组织损伤特点及IL-2对肠上皮损伤及修复作用及其机制尚未见报道。本文研究中子辐射后肠免疫组织病变特点及其对肠上皮再生调控作用，为其防治提供新思路。方法：采用2.5～5.5Gy中子及5.5-12Gyγ射线照射350只BALB／C小鼠和IEC-6细胞(正常SD大鼠空肠隐窝上皮细胞)，并用IL-2(25×10~3～1×10~5U／L)及JAK_1阻断剂A77-1726于照前12h或照后即刻处理细胞，分别于照后6h，12h，1～5d，7d，14d，21d及28d活杀取材或15min，30min，1h，3h，6h，9h，12h，1～3d收集细胞，采用光镜、电镜、免疫组化、MTT、FACS、免疫印迹等方法对比研究中子及γ射线照后肠免疫组织损伤、恢复规律和IL-2对IEC-6再生作用及其机制。结果：(1)肠免疫组织病理变化：中子组2.5Gy照后3d内，淋巴细胞发生凋亡、坏死，5d见再生，14～21d渐恢复，4.0和5.5Gy照后以坏死多见，未见明显恢复；γ射线组5.5Gy照后病变与中子2.5Gy组类似，但程度轻、再生早、凋亡多见，12Gy照后损伤程度介于中子4.0～5.5Gy组之间。(2)肠PP内T、B细胞及浆细胞变化：2.5Gy中子照后5d内，进行性减少，T／B比例升高，14d后恢复，其中T及浆细胞均呈量—效关系。(3)肠免疫因子变化：2.5Gy中子和5.5Gyγ射线照后5d内，IL-2，4及IgA均进行性减少，7～10d少量表达，14d后渐恢复，IFNγ，TGFβ_3，TNFα和IL-18于照后2d内进行性减少，3～7d增多，14d后恢复，均呈量—效关系。(4)IL-2对IEC-6作用及IL-2Rβ／JAK_1／STAT_5通路变化：中子4Gy照后3d内，，IEC-6增殖活力降低，照后1d凋亡和坏死增多，以坏死为主，γ射线4～12Gy照后1d以凋亡多见；给予IL-2后1～3d，IEC-6增殖活力提高，凋亡减少，且呈量—效关系，同时IL-2R表达增加，JAK_1激酶和转录因子STAT_5活化增强；IEC-6经A77-1726、IL-2与8Gyγ线共处理后24h增殖活力降低，STAT_5活化减弱。结论：(1)中子致肠免疫组织损伤重，恢复慢，损伤期凋亡与坏死并存，4.0和5.5Gy组以坏死为主，而γ射线照射以凋亡为主。(2)内源性IgA及肠上皮生长刺激因子IL-2、IL-4于中子损伤期减少，而生长抑制及凋亡诱导因子IFNγ，TGFβ，TNFα及IL-18于损伤期增多，进一步抑制肠上皮恢复。(3)4Gy中子照射抑制IEC-6增殖，以坏死损伤为重，而γ射线损伤以凋亡为主，IL-2可促进IEC-6增殖，抑其凋亡，活化JAK_1及STAT_5，A77-1726可抑制IL-2的促增殖及活化效应，IL-2可通过活化IL-2Rβ／JAK_1／STAT_5通路而介导其抗辐射效应。
[Abstract]:Objective: neutron radiation is more severe than 纬 -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 纬 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 纬-ray group after 5.5Gy irradiation were similar to those of neutron 2.5Gy group, and the pathological changes of 纬-ray group were similar to those of neutron 2.5Gy group, and the pathological changes of 纬-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 纬 -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- 伪 and IL-18 were gradually restored after 710 days of irradiation, and the levels of TGF- 尾 3- TNF- 伪 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- 伪 and TGF- 尾 3 TNF- 伪 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 纬 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 纬 -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 纬 TGF- 尾 TNF- 伪 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 纬 -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.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363

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