持续低氧对中枢神经免疫的调节

发布时间：2018-03-15 07:09

本文选题：低氧应激　切入点：冷应激、束缚应激　出处：《浙江大学》2005年博士论文　论文类型：学位论文

【摘要】：应激可以引起机体内环境平衡失调,导致生理乃至病理性变化,例如抑制机体免疫系统、影响神经系统的代谢和功能。低氧作为一种特殊的环境应激,使机体器官组织乃至细胞的供氧不足,造成全身性缺氧反应。许多研究指出缺氧和缺血性缺氧可抑制机体的免疫系统、抑制生长、抑制甲状腺轴和性腺轴的功能。低氧应激可以引起中枢性免疫变化,诱导神经内分泌变化,使中枢产生免疫分子并参与中枢神经系统的损伤、免疫炎症和发生缺血性疾病。然而关于低氧对中枢神经免疫作用的研究相对较少。因此,本文着重研究在持续性低氧应激下,中枢神经免疫的变化以及下丘脑神经肽促肾上腺皮质激素释放因子(CRF)、细胞因子—白细胞介素-6(IL-6)和ET-1表达的相关性。在神经—内分泌—免疫网络中,神经肽、激素和细胞因子的相互作用共同诱导应激下的中枢免疫过程。CRF不仅是应激下HPA轴的中枢始动者,而且CRF具有炎性因子的作用直接参与中枢免疫反应,此外还参与中枢神经系统的炎症和细胞因子的产生等免疫调节。由中枢神经系统内激活的神经胶质和神经元细胞产生的前炎性因子IL-6,是神经免疫调节的信号来源。在缺血性缺氧和脑疾患中,IL-6直接参与脑损伤病理过程,导致神经元细胞损伤、血脑屏障(BBB)的损坏、诱导脑水肿等免疫病理过程。脑内的炎性细胞因子同时影响血管舒缩活性物质的表达,例如内皮素(endothelin,ET)增加,引发血管收缩造成进一步缺血性脑损伤,脑内ET显著升高可以诱导神经细胞的损伤、引起脑水肿加剧。综上所述,应激下中枢的下丘脑、海马、视上核和室旁核等相关脑区内神经肽、细胞因子和神经递质的变化与中枢免疫调节密切相关。应激下HPA轴和IL-6、ET之间存在相互调节共同参与中枢免疫过程。
[Abstract]:Stress can cause imbalance of environmental balance in the body, leading to physiological and even pathological changes, such as inhibiting the body's immune system, affecting the metabolism and function of the nervous system. The lack of oxygen supply to organs, tissues and cells of the body, which results in a systemic anoxic response. Many studies have shown that hypoxia and ischemic hypoxia inhibit the immune system and growth of the body. Inhibiting the function of thyroid axis and gonadal axis. Hypoxia stress can induce central immune changes, induce neuroendocrine changes, produce immune molecules in the central nervous system and participate in the damage of the central nervous system. Immune inflammation and ischemic diseases. However, there are relatively few studies on the immune effects of hypoxia on central nervous system. The changes of central nervous system immunity and the correlation between the expression of hypothalamic neuropeptide corticotropin releasing factor (CRF), cytokine interleukin-6 (IL-6) and ET-1. In neuroendocrine immune networks, the interaction of neuropeptides, hormones and cytokines induces the central immune process under stress. CRF is not only the central initiator of the HPA axis under stress. Moreover, CRF has the effect of inflammatory factor directly involved in the central immune response. In addition, it also participates in the immune regulation of inflammation and cytokine production in the central nervous system. IL-6, a proinflammatory factor produced by the activated glial and neuronal cells in the central nervous system, is the signal source of neuroimmune regulation. IL-6 is directly involved in the pathological process of brain injury in ischemic hypoxia and brain diseases. The inflammatory cytokines in the brain also affect the expression of vasomotor and vasomotor active substances, such as endothelin et. Further ischemic brain injury is caused by vasoconstriction, and a significant increase in et in the brain can induce nerve cell damage and increase brain edema. The changes of neuropeptides, cytokines and neurotransmitters in the supraoptic nucleus and paraventricular nucleus are closely related to the central immune regulation.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

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