【摘要】：低氧/缺氧是指機(jī)體生命活動(dòng)所需的氧供應(yīng)不足,通常是由于吸入氣氧分壓過低、氧運(yùn)輸障礙或組織不能充分利用氧所引起。它是許多疾病可能共同存在的基本病理過程。低氧預(yù)適應(yīng)是目前提高機(jī)體對(duì)低氧耐受能力的主要途徑。目前,實(shí)施低氧預(yù)適應(yīng)的具體方法仍存在明顯的缺陷。有研究發(fā)現(xiàn),高壓氧(Hyperbaric oxygen,HBO)暴露的某些生物學(xué)效應(yīng)竟然與低氧類似。目前,高壓氧已成為臨床上一種實(shí)用而有效的治療手段。本工作設(shè)想,高壓氧暴露也可能產(chǎn)生誘導(dǎo)機(jī)體對(duì)低氧的耐受能力,本實(shí)驗(yàn)?zāi)康氖球?yàn)證這一假設(shè)和初步探討高壓氧暴露誘導(dǎo)低氧耐受的機(jī)制,從而為探索一種安全、有效和實(shí)用的以高壓氧暴露預(yù)防低氧損傷和提高機(jī)體對(duì)低氧耐受能力的新途徑提供實(shí)驗(yàn)依據(jù)。 低氧預(yù)適應(yīng)可使體內(nèi)活性氧物質(zhì)(Reactive oxygen species,ROS)的含量增加和清除能力增強(qiáng),這也是低氧預(yù)適應(yīng)增強(qiáng)機(jī)體對(duì)低氧耐受能力的重要機(jī)制之一。而一定壓力和時(shí)程的高壓氧暴露也能使體內(nèi)ROS增多。促紅細(xì)胞生成素(Erythropoietin,EPO)是發(fā)現(xiàn)最早并應(yīng)用于臨床的促造血細(xì)胞因子,其主要產(chǎn)生于腎臟和肝臟。近年來研究發(fā)現(xiàn),在其他組織,特別是中樞神經(jīng)系統(tǒng)也有EPO及其受體基因的表達(dá),而且EPO還具有較強(qiáng)的神經(jīng)營(yíng)養(yǎng)和保護(hù)作用。在低氧預(yù)適應(yīng)過程中,EPO通過增強(qiáng)外周血的攜氧能力,更重要的是作為中樞神經(jīng)營(yíng)養(yǎng)因子增強(qiáng)機(jī)體對(duì)低氧的耐受能力。還有研究表明,EPO含量變化受低氧誘導(dǎo)因子-1(Hypoxia inducible factor-1,HIF-1)調(diào)控。本實(shí)驗(yàn)室初步研究發(fā)現(xiàn),高壓氧反復(fù)暴露也能發(fā)揮類似低氧預(yù)適應(yīng)的作用,顯著提高小鼠對(duì)低氧環(huán)境的耐受能力。 基于以上研究結(jié)果設(shè)想:高壓氧暴露也可能通過類似低氧預(yù)適應(yīng)的某些途徑而增強(qiáng)機(jī)體對(duì)低氧的耐受能力。為此,主要進(jìn)行了以下研究工作:①觀察高壓氧暴露誘導(dǎo)低氧耐受的效應(yīng);②高壓氧暴露誘導(dǎo)低氧耐受機(jī)制的初步探討。 本研究主要獲得了以下結(jié)果:①高壓氧反復(fù)暴露結(jié)束后24h,小鼠低氧負(fù)重游泳力竭時(shí)間和急性低氧生存時(shí)間明顯延長(zhǎng);②高壓氧反復(fù)暴露結(jié)束后24h,小鼠血漿和腦內(nèi)丙二醛(MDA)含量增加;③高壓氧反復(fù)暴露結(jié)束后24h,外周血紅細(xì)胞計(jì)數(shù)(RCT)、血紅蛋白(HGB)、紅細(xì)胞比積(HCT)、和高熒光度網(wǎng)織紅百比率(HFR)均降低;④免疫組化檢測(cè)結(jié)果顯示高壓氧反復(fù)暴露結(jié)束后24h,腦內(nèi)皮層和海馬區(qū)EPO陽性細(xì)胞增多;Western blot檢測(cè)顯示高壓氧反復(fù)暴露結(jié)束后24h,皮層和海馬內(nèi)EPO蛋白含量明顯增多;⑤免疫組化和Western blot檢測(cè)顯示,高壓氧暴露結(jié)束即刻,小鼠腦內(nèi)HIF-1α增多,HIF-1α陽性細(xì)胞主要位于皮層和海馬區(qū)。 結(jié)論:①高壓氧暴露能明顯增強(qiáng)小鼠對(duì)低氧的耐受能力;②高壓氧暴露并未通
[Abstract]:Hypoxia / hypoxia refers to the insufficient supply of oxygen required by the body's vital activities, usually due to the low partial pressure of oxygen inhaled, the obstruction of oxygen transport or the inability of tissues to make full use of oxygen. It is the basic pathological process in which many diseases may co-exist. Hypoxia preconditioning is the main way to improve the tolerance to hypoxia. At present, the specific methods of implementing hypoxia preconditioning still have obvious defects. Some studies have found that some biological effects of hyperbaric oxygen (Hyperbaric oxygen,HBO) exposure are similar to hypoxia. At present, hyperbaric oxygen has become a practical and effective treatment. It is assumed that hyperbaric oxygen exposure may also induce tolerance to hypoxia. The purpose of this study was to verify this hypothesis and to explore the mechanism of hypoxia tolerance induced by hyperbaric oxygen exposure. An effective and practical new approach to prevent hypoxic injury and improve tolerance to hypoxia by hyperbaric oxygen exposure is provided. Hypoxia preconditioning can increase the content and scavenging ability of reactive oxygen (Reactive oxygen species,ROS) in vivo, which is one of the important mechanisms of hypoxia preconditioning to enhance hypoxia tolerance. Hyperbaric oxygen exposure at a certain pressure and duration also increased ROS in the body. Erythropoietin (Erythropoietin,EPO) is one of the earliest hematopoietic cytokines, which is mainly produced in kidney and liver. In recent years, it has been found that EPO and its receptor genes are also expressed in other tissues, especially in the central nervous system, and EPO also has strong neurotrophic and protective effects. During hypoxic preconditioning, EPO enhances the oxygen carrying capacity of peripheral blood and, more importantly, increases the tolerance to hypoxia as a central neurotrophic factor. Other studies have shown that the change of EPO content is regulated by hypoxia inducible factor-1 (Hypoxia inducible factor-1,HIF-1). Our preliminary study shows that repeated hyperbaric oxygen exposure can also play a similar role in hypoxic preconditioning and significantly improve the tolerance of mice to hypoxia. Based on the above results, it is assumed that hyperbaric oxygen exposure may also enhance the tolerance to hypoxia through some pathways similar to hypoxia preconditioning. For this reason, the following studies were carried out: (1) to observe the effects of hyperbaric oxygen exposure on hypoxia tolerance, and 2 to explore the mechanism of hypoxia tolerance induced by hyperbaric oxygen exposure. The main results of this study were as follows: (1) after repeated hyperbaric oxygen exposure, the exhaustion time and acute hypoxia survival time of mice with hypoxic load swimming were significantly prolonged 24 h after repeated hyperbaric oxygen exposure; (2) the content of malondialdehyde (MDA) in plasma and brain increased 24 hours after repeated hyperbaric oxygen exposure. 3After repeated hyperbaric oxygen exposure, the (RCT), hemoglobin (HGB), specific hematocrit (HCT),) and high fluorescence reticulocyte ratio (HFR) decreased 24 h after repeated exposure. (4) Immunohistochemical analysis showed that 24 hours after repeated hyperbaric oxygen exposure, the number of EPO positive cells increased in cerebral cortex and hippocampus, and the EPO protein content in cortex and hippocampus increased significantly 24 hours after repeated hyperbaric oxygen exposure. 5Immunohistochemistry and Western blot detection showed that HIF-1 偽 increased in the brain of mice at the end of hyperbaric oxygen exposure, and HIF-1 偽 positive cells were mainly located in cortex and hippocampus. Conclusion: (1) hyperbaric oxygen exposure can significantly enhance the tolerance to hypoxia in mice, and (2) hyperbaric oxygen exposure is not effective.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R363

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