本文選題：缺氧模型 + 肺組織��； 參考：《蘭州大學(xué)》2015年碩士論文

【摘要】：快速進(jìn)入高原環(huán)境時(shí),人們常會(huì)因?yàn)槿毖?出現(xiàn)惡心、嘔吐、乏力等一系列機(jī)體不適,嚴(yán)重者會(huì)出現(xiàn)急性高原疾病,如不及早治療可能會(huì)造成患者死亡。然而,急性高原疾病的發(fā)病機(jī)制不明確,造成藥物研發(fā)緩慢,使人們的生命健康安全遭受高原缺氧環(huán)境的威脅。因此,探究高原缺氧損傷機(jī)理,研發(fā)抗缺氧保護(hù)作用藥物非常重要。本論文將建立急進(jìn)高原實(shí)地缺氧大鼠模型,圍繞缺氧對(duì)大鼠體內(nèi)細(xì)胞因子的影響,探究高原環(huán)境對(duì)大鼠缺氧損傷的機(jī)制并考察抗炎藥物布洛芬的潛在抗缺氧保護(hù)作用。課題組首先通過急進(jìn)高原缺氧環(huán)境和高原低壓低氧模擬艙模擬,建立大鼠缺氧模型,比較缺氧組和平原組大鼠的血?dú)狻⑸�、病理差異。結(jié)果表明,急進(jìn)高原實(shí)地缺氧大鼠與高原低壓低氧模擬艙模擬缺氧大鼠的血?dú)�、生化、病理指�?biāo)變化趨勢(shì)基本一致,其中,急性缺氧(模擬缺氧和實(shí)地缺氧)對(duì)大鼠的主要損傷器官為肺組織。結(jié)果還提示,在涉及血?dú)�、生化測(cè)定的高原缺氧研究中,應(yīng)該對(duì)研究所用的缺氧模型做出選擇,不同模型的結(jié)果差異可能較大。本結(jié)果為急進(jìn)高原實(shí)地缺氧模型的建立提供實(shí)驗(yàn)依據(jù)。其次,采用Antibody Array技術(shù)比較高原缺氧組和平原組大鼠體內(nèi)34種大鼠細(xì)胞因子的差異,篩選獲得敏感細(xì)胞因子TIMP-1、MCP-1、TNF-α、IL-1β、 IFN-γ,并結(jié)合文獻(xiàn)報(bào)道和前期研究,采用Real-Time PCR(實(shí)時(shí)熒光定量PCR)和ELISA (酶聯(lián)免疫法)技術(shù),進(jìn)一步驗(yàn)證分析敏感細(xì)胞因子在肺組織中的基因相對(duì)表達(dá)量和蛋白含量。結(jié)果表明,高原組大鼠肺組織中TIMP-1、MCP-1、TNF-α、 IL-1β、IFN-γ的基因相對(duì)表達(dá)量分別升高2.09、5.23、1.66、1.75、2.57倍,蛋白含量分別升高61 J95%、51.01%、30.77%、12.64%、34.52%(P0.01)。最后,采用布洛芬干預(yù)急進(jìn)高原缺氧大鼠,比較平原組、高原組、布洛芬組和陽性對(duì)照藥(乙酰唑胺)組大鼠血?dú)狻⒉±碜兓?測(cè)定大鼠肺組織中TIMP-1、MCP-1、TNF-α、L-1β、IFN-γ的基因相對(duì)表達(dá)量和蛋白含量。結(jié)果表明,與高原組比較,布洛芬組缺氧大鼠動(dòng)脈血PaO2顯著性升高4.83%,動(dòng)脈血乳酸Lac顯著性降低51.20%(P0.01),大鼠肺組織損傷明顯減輕,高原布洛芬組大鼠肺組織中TIMP-1、MCP-1、TNF-α、IL-1β、IFN-γ的基因相對(duì)表達(dá)量均顯著性下降,蛋白含量分別顯著性降低4.75%、24.87%、28.09%、16.86%、14.21%、9.16%(P0.01)。本研究建立了急進(jìn)高原環(huán)境大鼠缺氧模型,采用Antibody Array技術(shù)篩選敏感細(xì)胞因子,并用ELISA和Real-Time PCR技術(shù)進(jìn)一步驗(yàn)證,利用抗炎藥物布洛芬干預(yù),得出以下結(jié)論：1、實(shí)地缺氧和模擬艙缺氧均會(huì)造成大鼠嚴(yán)重肺損傷,與平原組比較,兩者血?dú)�、生化、病理指�?biāo)變化趨勢(shì)基本一致,然而,兩個(gè)缺氧組之間的血?dú)�、生化指�?biāo)差異明顯；2、大鼠急性暴露缺氧環(huán)境,激活機(jī)體炎癥反應(yīng),促進(jìn)細(xì)胞因子TIMP-1、 MCP-1、TNF-α、IL-1β、IFN-γ的含量升高,進(jìn)一步擴(kuò)大炎癥反應(yīng),是缺氧刺激造成機(jī)體損傷的機(jī)制之一；3、布洛芬能夠減輕缺氧大鼠肺組織損傷,其保護(hù)作用機(jī)制可能與布洛芬提高缺氧大鼠Pa02和抑制細(xì)胞因子TIMP-1、MCP-1、TNF-α、IL-1β、IFN-γ的表達(dá)有關(guān)。
[Abstract]:Quickly enter the plateau environment, people often because of hypoxia, nausea, vomiting, weakness and a series of body discomfort, severe cases will lead to acute plateau disease, without early treatment may cause death. However, the pathogenesis of acute high altitude disease is not clear, resulting in drug development is slow, so that the life and health of the people safety suffers the plateau hypoxia environment threat. Therefore, exploring the mechanism of hypoxia injury research plateau, anti hypoxia and protective effect of drugs is very important. This paper will establish a rat model of hypoxia at high altitude field, on the effects of hypoxia on cytokines of rats in vivo, the potential protective effect of anti hypoxia on plateau environment on hypoxia injury in rats and the mechanism study of anti-inflammatory drug ibuprofen. Firstly the hypoxic environment at high altitude and high altitude simulation cabin simulation, establish the rat model of hypoxia, hypoxia group and comparison Blood gas, plain rats, biochemical, pathological differences. The results show that the gas field and high altitude hypoxia in rats at high altitude hypoxia simulation cabin to simulate hypoxia rat biochemical changes, pathological indicators are basically the same, among them, acute hypoxia (simulated hypoxia and hypoxia on the main organ damage field) of rat lung tissue. The results also showed that in blood biochemical research, hypoxia, hypoxia model should be used to study the choice of different models, different results may be larger. The results for the field at high altitude hypoxia model to provide experimental basis for establishing. Secondly, using Antibody Array technology to compare differences in plateau hypoxia group and plain rats in group 34 kinds of cytokines in rats, obtain sensitive cytokine TIMP-1, screening of MCP-1, TNF- alpha, IL-1 beta, IFN- gamma, and combined with the literature and previous studies, using Real-Time (real time PCR Fluorescence quantitative PCR) and ELISA (ELISA) technology, to further verify the analysis of relative expression of gene and protein content of sensitive cytokines in lung tissues. The results showed that the TIMP-1 group in the lung tissue of rats in the MCP-1 plateau, TNF- alpha, IL-1 beta, IFN- gamma gene relative expression quantity increased by 2.09,5.23,1.66,1.75,2.57 times respectively, protein content increased 61 J95%, respectively, 51.01%, 30.77%, 12.64%, 34.52% (P0.01). Finally, the ibuprofen intervention of acute high altitude hypoxia rats, compared with the plain group, plateau group, ibuprofen group and positive control drug (acetazolamide) rats, blood gas, pathological changes, the determination of TIMP-1 in rat lung tissue in MCP-1, TNF- alpha, L-1 beta, relative expression and protein content of IFN- gamma gene. The results showed that compared with the plateau group, arterial blood PaO2 ibuprofen group in hypoxic rats significantly increased 4.83%, arterial blood lactic acid Lac significantly decreased 51.20% (P0.01), lung tissue of rats The damage was significantly reduced, TIMP-1 group lung tissue of rats in plateau ibuprofen MCP-1, TNF- alpha, IL-1 beta, IFN- gamma gene relative expression were significantly decreased, protein content were significantly decreased by 4.75%, 24.87%, 28.09%, 16.86%, 14.21%, 9.16% (P0.01). This study established in rats at high altitude environment hypoxia model, Screening Sensitive cytokines by Antibody Array technology, and further confirmed by ELISA and Real-Time PCR technology, the use of anti-inflammatory drugs ibuprofen intervention, draw the following conclusions: 1. Hypoxia and hypoxia field simulation cabin will cause serious lung injury in rats, compared with the plain group both blood biochemical, pathological change trend index basically the same, however, the blood gas between the two hypoxia group, biochemical index significantly; 2, acute exposure to hypoxia in rats, the activation of the inflammatory reaction, promote cell factor TIMP-1, MCP-1, TNF- alpha, IL-1 beta, gamma IFN- content Increased, further expand the inflammatory reaction is hypoxia caused by one of the mechanisms of body injury; 3, ibuprofen can reduce the lung tissue hypoxia injury in rats, the protective effect and possible mechanism of ibuprofen increased in hypoxic rats Pa02 and inhibition of cytokine TIMP-1, MCP-1, TNF- alpha, IL-1 beta, the expression of IFN- gamma.

【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R594.3

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