發(fā)布時間：2019-06-19 14:10

【摘要】：低氧是指機體生命活動所需的氧不能得到充足的供給,通常是由于吸入氣氧分壓過低、氧運輸障礙或組織不能充分利用氧所引起。低氧可誘發(fā)機體各系統(tǒng)功能改變,威脅人體健康。它是多種疾病如心、肺疾病、中風(fēng)及腫瘤的主要病理生理反應(yīng)。另外,劇烈運動及高原居住的人群均面臨著低氧的問題。 經(jīng)典的誘導(dǎo)低氧耐受方法為低氧預(yù)適應(yīng),不論是人還是動物,通過低氧預(yù)適應(yīng)均可獲得對低氧一定程度的耐受,但低氧預(yù)適應(yīng)具體處理措施也存在不足。低氧預(yù)適應(yīng)誘導(dǎo)低氧耐受的機制,一直是低氧研究領(lǐng)域的熱點之一,盡管取得了許多進展,但具體機制尚未完全明了。 低氧誘導(dǎo)因子-1(hypoxia-inducible factor-1,HIF-1)在低氧預(yù)適應(yīng)誘導(dǎo)低氧耐受的機制中發(fā)揮極其重要的作用。HIF-1蛋白是由a亞單位(HIF-1a)與β亞單位(HIF-1β)組成的二聚體,是氧平衡調(diào)控的管家調(diào)節(jié)因子。低氧環(huán)境下它可通過調(diào)節(jié)其下游基因的轉(zhuǎn)錄來促進機體血管及紅細胞的生成、增強糖酵解及葡萄糖轉(zhuǎn)運,使機體產(chǎn)生低氧耐受。HIF-1與DNA結(jié)合首先要求HIF-1a與HIF-1β形成二聚體,HIF-1a蛋白水平是HIF-1 DNA結(jié)合活性的主要決定因素。HIF-1a蛋白水平主要受氧分壓調(diào)節(jié),同時也受過渡金屬、一氧化氮(nitric oxide,NO)、活性氧(reactive oxygenspecies,ROS)、細胞因子及機械應(yīng)力等因素影響。 表面上看,高壓氧(hyperbaric oxygen,HBO)和低氧對機體的影響截然相反,前者可提高體內(nèi)氧和二氧化碳含量,后者則會降低體內(nèi)氧和二氧化碳含量。實際上,HBO和低氧對機體的影響有許多相似之處。比如,兩者都可抑制能量代謝,降低腦內(nèi)ATP含量,增加體內(nèi)自由基(free radical,FR)和H~+含量,并對機體產(chǎn)生損害,甚至導(dǎo)致個體死亡。HBO和低氧適應(yīng)性暴露都可增強機體抗氧化損傷的能力,預(yù)防動物慢性氧中毒,減輕中樞神經(jīng)系統(tǒng)(central nervous system,CNS)缺血性損傷,提高CNS對HBO的敏感性。這些現(xiàn)象提示,HBO適應(yīng)性暴露可能具有提高機體耐受低氧損傷的能力,可能是一種低氧預(yù)適應(yīng)的替代方案。 根據(jù)上述現(xiàn)象,我們推測HBO暴露可能具有誘導(dǎo)機體低氧耐受的效應(yīng)。作為一種治療手段,HBO已廣泛應(yīng)用于臨床上缺血性疾病、休克、一氧化碳中毒、氣栓癥及減壓病等疾病的治療。由于HBO治療方法比低氧預(yù)適應(yīng)時間短、安全性高,如果這一方法確實有效,必將為臨床醫(yī)學(xué)、高原醫(yī)學(xué)、運動醫(yī)學(xué)及軍事醫(yī)學(xué)中低氧問題提供一個新的解決途徑。
[Abstract]:Hypoxia refers to the fact that the oxygen needed for life activities of the body can not be adequately supplied, which is usually caused by the low partial pressure of oxygen in inhaled gas, the obstacle of oxygen transport or the inability of tissues to make full use of oxygen. Hypoxia can induce changes in the functions of various systems and threaten human health. It is the main pathophysiological reaction of many diseases such as heart, lung disease, stroke and tumor. In addition, strenuous exercise and people living at high altitude are facing the problem of hypoxia. The classical method of inducing hypoxia tolerance is hypoxia pretreatment, which can be used to obtain a certain degree of tolerance to hypoxia in both human and animals, but there are also some shortcomings in the specific treatment measures of hypoxia tolerance. The mechanism of hypoxia tolerance induced by hypoxia pretreatment has always been one of the hotspots in the field of hypoxia research. although a lot of progress has been made, the specific mechanism has not been fully understood. Hypoxia inducible factor-1 (hypoxia-inducible factor-1,HIF-1) plays an important role in the mechanism of hypoxia tolerance induced by hypoxia pretreatment. HIF-1 protein is a dimer composed of a subunit (HIF-1a) and 尾 subunit (HIF-1 尾), which is a housekeeper regulator of oxygen balance regulation. In hypoxia environment, it can promote the production of blood vessels and red blood cells by regulating the transcription of its downstream genes, enhance glycolysis and glucose transport, and make the body produce hypoxia tolerance. The binding of HIF-1a-1 to DNA first requires the formation of dimer between HIF-1 and HIF-1 尾, and HIF-1a protein level is the main determinant of HIF-1 DNA binding activity. HIF-1a protein level is mainly regulated by oxygen partial pressure, but also by transition metal. Nitric oxide (nitric oxide,NO), reactive oxygen species (reactive oxygenspecies,ROS), cytokines and mechanical stress. On the surface, hyperbaric oxygen (hyperbaric oxygen,HBO) and hypoxia have the opposite effect on the body. The former can increase the content of oxygen and carbon dioxide in the body, while the latter can reduce the content of oxygen and carbon dioxide in the body. In fact, there are many similarities between the effects of HBO and hypoxia on the body. For example, both of them can inhibit energy metabolism, decrease the content of ATP in the brain, increase the content of free radicals (free radical,FR) and H ~, and cause damage to the body, and even lead to individual death. Free radical,FR and hypoxia adaptive exposure can enhance the ability of antioxidant damage, prevent chronic oxygen poisoning in animals, reduce (central nervous system,CNS ischemic damage in central nervous system, and increase the sensitivity of CNS to HBO. These phenomena suggest that HBO adaptive exposure may improve the ability of the body to withstand hypoxia injury, and may be an alternative to hypoxia pretreatment. According to the above phenomena, we speculate that HBO exposure may have the effect of inducing hypoxia tolerance. As a treatment, HBO has been widely used in the treatment of ischemic diseases, shock, carbon monoxide poisoning, air embolism and decompression sickness. Because the treatment time of HBO is shorter and the safety is higher than that of hypoxia, if this method is really effective, it will provide a new way to solve the problem of hypoxia in clinical medicine, altitude medicine, sports medicine and military medicine.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2005
【分類號】：R363

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