高压氧诱导机体低氧耐受机制的初步研究
发布时间：2018-12-16 18:04
【摘要】：低氧/缺氧是指机体生命活动所需的氧供应不足,通常是由于吸入气氧分压过低、氧运输障碍或组织不能充分利用氧所引起。它是许多疾病可能共同存在的基本病理过程。低氧预适应是目前提高机体对低氧耐受能力的主要途径。目前,实施低氧预适应的具体方法仍存在明显的缺陷。有研究发现,高压氧(Hyperbaric oxygen,HBO)暴露的某些生物学效应竟然与低氧类似。目前,高压氧已成为临床上一种实用而有效的治疗手段。本工作设想,高压氧暴露也可能产生诱导机体对低氧的耐受能力,本实验目的是验证这一假设和初步探讨高压氧暴露诱导低氧耐受的机制,从而为探索一种安全、有效和实用的以高压氧暴露预防低氧损伤和提高机体对低氧耐受能力的新途径提供实验依据。 低氧预适应可使体内活性氧物质(Reactive oxygen species,ROS)的含量增加和清除能力增强,这也是低氧预适应增强机体对低氧耐受能力的重要机制之一。而一定压力和时程的高压氧暴露也能使体内ROS增多。促红细胞生成素(Erythropoietin,EPO)是发现最早并应用于临床的促造血细胞因子,其主要产生于肾脏和肝脏。近年来研究发现,在其他组织,特别是中枢神经系统也有EPO及其受体基因的表达,而且EPO还具有较强的神经营养和保护作用。在低氧预适应过程中,EPO通过增强外周血的携氧能力,更重要的是作为中枢神经营养因子增强机体对低氧的耐受能力。还有研究表明,EPO含量变化受低氧诱导因子-1(Hypoxia inducible factor-1,HIF-1)调控。本实验室初步研究发现,高压氧反复暴露也能发挥类似低氧预适应的作用,显著提高小鼠对低氧环境的耐受能力。 基于以上研究结果设想:高压氧暴露也可能通过类似低氧预适应的某些途径而增强机体对低氧的耐受能力。为此,主要进行了以下研究工作:①观察高压氧暴露诱导低氧耐受的效应;②高压氧暴露诱导低氧耐受机制的初步探讨。 本研究主要获得了以下结果:①高压氧反复暴露结束后24h,小鼠低氧负重游泳力竭时间和急性低氧生存时间明显延长;②高压氧反复暴露结束后24h,小鼠血浆和脑内丙二醛(MDA)含量增加;③高压氧反复暴露结束后24h,外周血红细胞计数(RCT)、血红蛋白(HGB)、红细胞比积(HCT)、和高荧光度网织红百比率(HFR)均降低;④免疫组化检测结果显示高压氧反复暴露结束后24h,脑内皮层和海马区EPO阳性细胞增多;Western blot检测显示高压氧反复暴露结束后24h,皮层和海马内EPO蛋白含量明显增多;⑤免疫组化和Western blot检测显示,高压氧暴露结束即刻,小鼠脑内HIF-1α增多,HIF-1α阳性细胞主要位于皮层和海马区。 结论:①高压氧暴露能明显增强小鼠对低氧的耐受能力;②高压氧暴露并未通
[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 伪 increased in the brain of mice at the end of hyperbaric oxygen exposure, and HIF-1 伪 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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363
本文编号：2382804
[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 伪 increased in the brain of mice at the end of hyperbaric oxygen exposure, and HIF-1 伪 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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363
【参考文献】
相关期刊论文 前1条
1 朱全，，浦钧宗;大鼠游泳训练在运动实验中的应用方法[J];中国运动医学杂志;1996年02期
本文编号：2382804
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