一氧化氮在高压氧诱导低氧耐受中的作用

发布时间：2018-02-27 06:06

本文关键词： 高压氧低氧低氧耐受一氧化氮一氧化氮合酶　出处：《第二军医大学》2006年硕士论文　论文类型：学位论文

【摘要】：低氧是多种疾病如心、肺疾病、中风及肿瘤的主要病理生理反应。经典的诱导低氧耐受的方法为低氧预适应。大量研究表明,高压氧(hyperbaric oxygen,HBO)和低氧适应性暴露都可增强机体抗氧化损伤的能力、预防动物慢性氧中毒、减轻中枢神经系统(central nervous system,CNS)缺血性损伤、提高CNS对HBO的敏感性。同时,我们研究发现,HBO适应性暴露可提高机体耐受低氧损伤的能力,但其诱导机制尚不清楚。一氧化氮(nitric oxide,NO)是一种高生物活性的气体分子,在体内发挥多种生物学效应,如神经调节、舒张血管、细胞再生,尤其是在改善脑血流、神经保护方面发挥重要作用,对脑缺血缺氧具有保护作用。一氧化氮合酶(nitric oxide synthase,NOS)在体内可催化精氨酸生成NO和胍氨酸,NOS的含量及活性直接影响体内NO的含量。 NOS活性增强,NO生成增多可能通过以下几种途径发挥对缺血缺氧脑组织损伤的保护作用:(1)舒张血管:NO通过与血管平滑肌细胞内可溶性鸟苷酸环化酶(soluble guanylyl cyclase,sGC)结合,引起细胞内环磷酸鸟苷(cyclic GMP,cGMP)增加并进一步激活其下游信号转导途径而最终引起血管舒张。同时,NO还能阻止去甲肾上腺素和5-羟色胺等物质所引发的脑动脉收缩反应。(2)信息传递:脑动脉由非肾上腺素能非胆碱能(NANC)神经支配,NANC神经末梢释放的NO在NANC神经与脑血管平滑肌之间的信息传递中起着重要的作用。(3)维持血管正常结构:主要通过抑制血管平滑肌增殖,抑制血小板、白细胞的粘附和聚集,保护脑血管内皮而发挥作用。(4)与低氧诱导因子-1(hypoxia-inducible factor-1,
[Abstract]:Hypoxia is the main pathophysiological response of many diseases such as heart, lung, stroke and tumor. The classical method of inducing hypoxia tolerance is hypoxic preconditioning. Hyperbaric oxygen (HBO) and hypoxic adaptive exposure can enhance the ability of antioxidant injury, prevent chronic oxygen poisoning in animals, alleviate central nervous system central nervous system ischemic damage, and enhance the sensitivity of CNS to HBO. We found that adaptive exposure to HBO can improve the ability of tolerance to hypoxia injury, but the mechanism of its induction is not clear. Nitric oxide nitric oxide (no) is a highly bioactive gas molecule that plays many biological effects in the body, such as nerve regulation, vasodilation, cell regeneration, especially in improving cerebral blood flow and neuroprotection. Nitric oxide synthase (NOS) can catalyze arginine to produce no and guanidine acid. The enhancement of NOS activity and the increase of no production may play a protective role against ischemic and hypoxic brain tissue injury in the following ways: 1) vasodilator 1) vasodilator: no binds to soluble guanylyl cyclase in vascular smooth muscle cells (VSMCs). It also increases and further activates its downstream signal transduction pathway and eventually results in vasodilation. At the same time, no can prevent the contractility of cerebral artery induced by norepinephrine and serotonin, and other substances, such as norepinephrine and serotonin. (2) Information transduction: the cerebral artery innervated by non-adrenergic, non-cholinergic, NANC- (no) released from the nerve endings of the NANCs plays an important role in the transmission of information between the NANC nerve and the vascular smooth muscle. Mainly by inhibiting the proliferation of vascular smooth muscle, Inhibiting the adhesion and aggregation of platelets, leukocytes, and protecting cerebrovascular endothelium. 4) and hypoxia-inducible factor-1, a hypoxia-inducible factor-1, a hypoxia-inducible factor-1, and hypoxia-inducible factor-1.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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