本文關(guān)鍵詞： 腸 缺血/再灌注 損傷 低氧誘導(dǎo)因子-1α 微小核糖核酸-21　出處：《南京醫(yī)科大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：研究背景:腸缺血/再灌注(Ischemia/Reperfusion,I/R)損傷可導(dǎo)致腸組織損傷,即腸I/R損傷,缺血后處理是指組織器官在較長時間缺血后,在再灌注一開始即進行3個循環(huán)的再灌注/停灌注處理,即30秒再灌注/30秒再阻斷,雖然已經(jīng)證實缺血后處理可以減輕腸I/R損傷的程度,但是缺血后處理抗腸I/R損傷的機制尚不明確。目的:研究低氧誘導(dǎo)因子-1α(HIF-1α)和微小核糖核酸-21(miR-21)在缺血后處理抗腸I/R損傷中的作用和機制,揭示缺血后處理抗腸I/R損傷的發(fā)生機制,從而為臨床治療腸I/R損傷提供理論依據(jù)。資料和方法:本研究首先通過IEC-6細(xì)胞進行系列體外實驗研究,主要步驟和內(nèi)容包括:1.IEC-6細(xì)胞的體外培養(yǎng);2.缺氧環(huán)境模擬缺血、缺氧,缺氧/復(fù)氧模擬I/R;3.不同條件下觀察HIF1-α和miR-21的表達水平;然后通過大鼠腸I/R損傷模型進行系列的體內(nèi)實驗研究,主要步驟和內(nèi)容包括:1.動物模型制備;2.給予相關(guān)干預(yù)措施,并制備標(biāo)本;3.對相關(guān)觀察指標(biāo)進行檢測。結(jié)果:通過大鼠腸I/R損傷的動物模型,研究發(fā)現(xiàn):缺血后處理誘導(dǎo)HIF-1α和miR-21的表達水平顯著升高,降低腸I/R損傷評分,并降低腸上皮細(xì)胞凋亡指數(shù)。阻斷HIF-1α后,miR-21的表達水平下降,并且缺血后處理抗腸I/R損傷的作用消失,證實miR-21的表達是由HIF1-α調(diào)控的,且HIF-Iα和miR-21參與了缺血后處理抗腸I/R損傷的作用。腸上皮細(xì)胞IEC-6研究證實:缺氧可誘導(dǎo)miR-21的表達水平顯著升高,但在阻斷HIF1-α后,缺氧誘導(dǎo)miR-21的表達水平升高的作用消失,證實miR-21的表達是由HIF1-α調(diào)控的;同時,阻斷miR-21或HIF1-α后,miR-21調(diào)控程序性細(xì)胞死亡4(PDCD4)和Fas-L的作用消失,進而導(dǎo)致缺血后處理抗腸I/R損傷的作用消失。結(jié)論:缺血后處理通過作用于HIF1-α進而調(diào)控miR-21的表達,miR-21可以通過調(diào)控PDCD4和Fas-L進而調(diào)控細(xì)胞的凋亡。缺血后處理通過調(diào)控HIF1-α和miR-21而減輕腸I/R損傷的程度。
[Abstract]:Background: Ischemia / reperfusion Ischemia / reperfusion I / R injury may lead to intestinal tissue damage, I. E. intestinal I / R damage. Post-ischemic treatment refers to the tissue and organs after a long period of ischemia, at the beginning of reperfusion three circulatory reperfusion / reperfusion treatment, that is, 30 seconds reperfusion / 30 seconds reperfusion block. Although it has been shown that ischemic post-treatment can reduce the extent of intestinal I / R damage. But the mechanism of intestinal I / R injury after ischemic treatment is not clear. Objective: to study hypoxia inducible factor-1 偽 (HIF-1 偽) and microRNA (-21miR-21). The role and mechanism of intestinal I / R injury after ischemic treatment. To reveal the mechanism of intestinal I / R injury induced by ischemic postconditioning. In order to provide a theoretical basis for the clinical treatment of intestinal I / R injury. Materials and methods: this study first carried out a series of in vitro experiments through IEC-6 cells. The main steps and contents include: 1. In vitro culture of IEC-6 cells; 2. Anoxic environment to simulate ischemia, hypoxia, hypoxia / reoxygenation to simulate I / R; 3. The expression levels of HIF1- 偽 and miR-21 were observed under different conditions. Then a series of in vivo experiments were carried out on the rat intestinal I / R injury model. The main steps and contents included: 1. 2. Relevant intervention measures were given, and specimens were prepared. 3.Results: through the animal model of intestinal I / R injury, we found that the expression levels of HIF-1 偽 and miR-21 were significantly increased after ischemic treatment. After blocking HIF-1 偽, the expression of miR-21 decreased, and the effect of ischemic treatment on intestinal I / R injury disappeared. It is confirmed that the expression of miR-21 is regulated by HIF1- 偽. HIF-I 偽 and miR-21 were involved in the protective effect on intestinal I / R injury after ischemia. IEC-6 studies of intestinal epithelial cells confirmed that hypoxia could induce a significant increase in the expression of miR-21. However, after blocking HIF1- 偽, the effect of hypoxia induced increased expression of miR-21 disappeared, which confirmed that the expression of HIF1- 偽 was regulated by HIF1- 偽. At the same time, after blocking miR-21 or HIF1- 偽, the effects of miR-21 on programmed cell death (4pPDCD4) and Fas-L disappeared. Conclusion: the expression of miR-21 is regulated by the action of HIF1- 偽 in the ischemic post-treatment. [WT5HZ] [WT5 "HZ] [WT5" BZ] [WT5 "BZ] [WT5BZ]. MiR-21 can regulate apoptosis by regulating PDCD4 and Fas-L, and post-ischemic treatment can reduce the degree of intestinal I / R damage by regulating HIF1- 偽 and miR-21.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R574

【參考文獻】

相關(guān)期刊論文 前5條

1 María Isabel Taborda;Sebastián Ramírez;Giuliano Bernal;;Circular RNAs in colorectal cancer: Possible roles in regulation of cancer cells[J];World Journal of Gastrointestinal Oncology;2017年02期

2 Carlos Rodrigo Camara-Lemarroy;;Remote ischemic preconditioning as treatment for non-ischemic gastrointestinal disorders: Beyond ischemia-reperfusion injury[J];World Journal of Gastroenterology;2014年13期

3 Yu-Feng Liao;Wei Zhu;Dong-Pei Li;Xiao Zhu;;Heme oxygenase-1 and gut ischemia/reperfusion injury: A short review[J];World Journal of Gastroenterology;2013年23期

4 ;Changes of microvascular architecture,ultrastructure and permeability of rat jejunal villi at different ages[J];World Journal of Gastroenterology;2003年04期

5 呂藝,盛志勇,黎君友,孫小慶,晉樺,姜小國;腸缺血-再灌流大鼠小腸血管內(nèi)皮細(xì)胞ICAM-1表達的變化及其與腸損傷的關(guān)系[J];中華普通外科雜志;2000年03期

，

本文編號：1487441