本文選題：腸三葉因子 + 新生兒壞死性小腸結(jié)腸炎��； 參考：《武漢大學(xué)》2009年博士論文

【摘要】：目的：研究腸三葉因子(ITF)對壞死性小腸結(jié)腸炎(NEc)新生大鼠的腸粘膜中促炎細胞因子(IL-1β,IL-6)和抗炎細胞因子(IL-10)含量的影響,以及對NEC新生大鼠中核因子-κB(NF-κB)的活化及胞內(nèi)分布規(guī)律；觀察MAPK通路在新生大鼠NEC模型發(fā)病中的作用,探討ITF對NEC保護作用機制。 方法：50只新生鼠隨機分為5組(A、B、C、D、E),每組10只：A組為正常對照組,未進行缺氧、低溫及注射用藥；B組為正常組予以皮下注射ITF0.2mg(0.2m1)；C組為NEC模型后未進行注射用藥；D組為NEC模型后予以皮下注射生理鹽0.2ml；E組為NEC模型后予以皮下注射ITF0.2mg(0.2m1)。并于NEC模型后第4天處死并取回盲部腸組織1-2cm固定、包埋、切片、HE染色拍照觀察組織學(xué)變化及免疫組化觀察NF-κB及MAPK通路的表達,其它腸組織制備組織勻漿,取上清液檢測IL-1p、IL-6、IL-10含量。 結(jié)果：NEC模型后給藥E組病理組織學(xué)改變積分范圍從0-2分,與正常對照組相比,粘膜下層或固有層有輕度分離,而模型組C、D組病理組織學(xué)改變積分范圍從2-4分,有粘膜下層或固有層有重度分離,粘膜下層和肌層有嚴(yán)重水腫,該區(qū)的絨毛崩解分離和絨毛的缺血壞死。NEC模型后給藥E組腸粘膜組織勻漿IL-1β含量明顯低于模型組C、D(P0.01)而與正常組A、B組無顯著性差異(P0.05)。NEC模型后給藥E組腸粘膜組織勻漿IL-6含量明顯低于模型組C、D(P0.01)而與正常組A、B組無顯著性差異(P0.05)。E組IL-10含量明顯高于C、D組(P0.01)和A、B組(P0.01)；新生大鼠NEC模型中腸上皮細胞NF-κB(p65)陽性表達,陽性顆粒數(shù)和染色強度明顯高于陰性對照和正常組；新生大鼠NEC模型中皮下注射ITF后腸組織NF-κB9(p65)呈弱陽性表達,與免疫組化染色陰性對照和正常組相比呈陽性,但與NEC模型組NF-KB(p65)陽性表達相比明顯減弱；新生大鼠NEC模型后MAPK通路中MEK/ERK/Elk-1, JNK/c-Jun以及p38均發(fā)生磷酸化激活；予以ITF治療新生大鼠NEC模型中發(fā)現(xiàn),JNK/c-Jun和p38表達較NEC模型組無明顯升高,而MEK/ERK/Elk-1通路則顯著激活。 結(jié)論：1)ITF可能是抑制促炎細胞因子(IL-1β,IL-6)的表達和促進抗炎細胞因子(IL-10)的合成,并通過抑制NF-κB信號通路,從而抑制其代謝合成產(chǎn)物的生成,減少細胞炎癥因子的升高,進而減輕小腸結(jié)腸組織炎癥反應(yīng),達到了保護腸粘膜的作用；2)新生大鼠NEC模型后MAPK通路中MEK/ERK/Elk-1, JNK/c-Jun以及p38均發(fā)生磷酸化激活,該結(jié)果提示MAPK參與NEC發(fā)病過程；予以ITF治療新生大鼠NEC模型中發(fā)現(xiàn),JNK/c-Jun和p38表達較NEC模型組無明顯升高,而MEK/ERK/Elk-1通路則顯著激活,該結(jié)果提示了ITF可能是通過MAPK中MEK/ERK/Elk-1通路發(fā)揮對新生NEC大鼠的治療作用
[Abstract]:Objective: to study the effects of intestinal trefoil factor (ITF) on the contents of proinflammatory cytokine (IL-1 尾 -IL-6) and anti-inflammatory cytokine (IL-10) in the intestinal mucosa of nec rats, and on the activation and intracellular distribution of nuclear factor- 魏 B NF- 魏 B in neonatal rats with NEC. To observe the role of MAPK pathway in the pathogenesis of NEC in neonatal rats and to explore the protective mechanism of ITF on NEC. Methods Fifty newborn mice were randomly divided into 5 groups, 10 in each group as normal control group without hypoxia. The hypothermia group and the control group were subcutaneously injected with ITF 0.2 mg / m ~ (-1) NEC model. Group D was treated by subcutaneous injection of physiological salt 0.2ml / ml NEC model and then subcutaneous injection of ITF _ (0.2) mg ~ (-1) ~ (0.2) mg ~ (-1) after subcutaneous injection of ITF _ (0.2) mg ~ (-1) ~ (-1). On the 4th day after NEC model, the 1-2cm was fixed and embedded in the intestinal tissue of the blind part. The histological changes and the expression of NF- 魏 B and MAPK pathway were observed by HE staining and immunohistochemistry. The homogenate of other intestinal tissues was prepared. The supernatant was used to detect the level of IL-6 and IL-10 in the supernatant. Results the score of histopathological changes in group E was 0-2 points after the administration of the control group. Compared with the normal control group, the submucous layer or lamina propria was slightly separated, while the score of histopathological changes in group C was 2-4 points. The submucosa or lamina propria has severe separation, and the submucous and muscular layers have severe edema. The content of IL-1 尾 in intestinal mucosa homogenate of group E was significantly lower than that of group C (P < 0.01), but there was no significant difference between group A and group A (P 0.05). The content of IL-6 in plasma was significantly lower than that in model group (P 0.01), but there was no significant difference between group A and group A (P 0.05). The content of IL-10 in group E was significantly higher than that in group C (D) and group A (P 0.01), and the positive expression of NF- 魏 Bp65) in intestinal epithelial cells in neonatal rat model of NEC. The number and intensity of positive granules were significantly higher than those of negative control and normal group, and the expression of NF- 魏 B9 p65 in intestinal tissue after subcutaneous injection of ITF was weakly positive in neonatal rat model of NEC, and was positive compared with that of negative control group and normal group by immunohistochemical staining. However, compared with the NEC model group, the expression of NF-KBP p65) was significantly decreased, the expression of MEK / ERK / Elk-1, JNK/c-Jun and p38 was activated in the MAPK pathway of neonatal rats after NEC model, and the expression of JNKP / c-Jun and p38 in NEC model of neonatal rats treated with ITF was not significantly higher than that in NEC model group. The MEK/ERK/Elk-1 pathway was significantly activated. Conclusion 1 / 1 ITF may inhibit the expression of pro-inflammatory cytokine IL-1 尾 -IL-6 and promote the synthesis of anti-inflammatory cytokine (IL-10). It may inhibit the production of its metabolites and decrease the increase of cytokines by inhibiting the signal pathway of NF- 魏 B. Then the inflammatory reaction of intestinal colon tissue was alleviated and the intestinal mucosa was protected. (2) phosphorylation of MEK / ERK / Elk-1, JNK/c-Jun and p38 in MAPK pathway was observed in neonatal rat NEC model. The results suggested that MAPK was involved in the pathogenesis of NEC. The expression of JNKc-Jun and p38 in neonatal rats treated with ITF was not significantly higher than that in NEC model group, but the MEK/ERK/Elk-1 pathway was significantly activated. The results suggest that ITF may play a therapeutic role in neonatal NEC rats through MEK/ERK/Elk-1 pathway in MAPK.
【學(xué)位授予單位】：武漢大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2009
【分類號】：R725.7;R-332

【參考文獻】

相關(guān)期刊論文 前1條

1 ;MAPK signal pathways in the regulation of cell proliferation in mammalian cells[J];Cell Research;2002年01期

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本文編號：1966252