模拟高原环境大脑皮质及血脑屏障的病理变化与AQP4的相关性实验研究

发布时间：2018-01-12 14:39

本文关键词：模拟高原环境大脑皮质及血脑屏障的病理变化与AQP4的相关性实验研究　出处：《第三军医大学》2005年硕士论文　论文类型：学位论文

【摘要】：人或动物从低海拔急进高原,暴露于低压低氧寒冷环境可能发生系列病理反应,表现为头痛、恶心、呕吐、失眠、疲乏、头昏眼花、共济失调等,称高山反应,也称急性高原病(acute mountain sickness,AMS)。有报道说人进入2,500 米以上高原就可能发生高原反应。AMS 重者发生高原肺水肿(high altitude pulmonary edema,HAPE)或高原脑水肿(high altitude cerebral edema,HACE),表现为呼吸困难、精神智力障碍以至昏迷。HACE 是急性高原病的极端严重情况,如不及早预防和救治,危及患者生命。现代交通和旅游业的发达,社会交流的增多,有越来越多的人进入高原地区,因此,高原病的防治愈加重要和迫切。已有研究认为,急性高原病和HACE 的主要病变是血管源性脑水肿和颅内高压,但到目前为止对高原脑水肿发生的细胞和分子机制仍知之甚少。胶质细胞足板是血脑屏障(blood brain barrier,BBB)的重要结构成分,近年在创伤、缺血、肿瘤性脑水肿的研究中发现,胶质细胞(及其突起、胶质足)形态学变化先于神经元,认为是最早的病理反应,但胶质细胞在AMS 和HACE 中的反应变化还未见研究报告。水通道蛋白是水分子跨膜运动的主要分子基础,在调节脑水平衡中起着关键作用,认为在病理生理过程中也发挥主要作用,是目前研究的热点,AQP4在AMS 和HACE 发生中的作用值得探讨。在高原反应、AMS 和HACE 情况下BBB 的病理变化、胶质细胞反应、AQP4及其mRNA 的表达变化,以及他们之间的相互关系还未见研究报道,本实验通过急进高原5000m 大鼠动物模型,观察4h~4w 这些指标的改变,以探索高原反应/AMS 和HACE 的发病机制。实验结果如下: 1.一般情况:实验组大鼠4h~72h 活动度减少,蛛网膜、肺组织、胃肠明显充血。以后活动增加,进食有所增加,组织充血减轻至接近正常。 2.光镜观察:实验组24h、48h 及72h 蛛网膜轻度充血,脑组织微血管周围间隙增宽。2w、4w 时胶质细胞有增生现象,有胶质结节形成。
[Abstract]:People or animals from low altitude into the plateau, exposure to low pressure hypoxia cold environment may occur a series of pathological reactions, such as headache, nausea, vomiting, insomnia, fatigue, dizziness, ataxia, and so on, known as mountain reaction. Also known as acute high altitude disease (AMS). It has been reported that people enter 2. High altitude pulmonary edema may occur in patients with high altitude reaction. Hape) or high altitude cerebral HACEE showed dyspnea. Mental retardation and even coma. HACE is an extremely serious condition of acute altitude disease, such as early prevention and treatment, endangering the life of patients, the development of modern transportation and tourism, and the increase of social communication. More and more people enter plateau area, therefore, the prevention and cure of altitude disease is more and more important and urgent. It has been suggested that the main lesions of acute high altitude disease and HACE are vasogenic brain edema and intracranial hypertension. But up to now, little is known about the cellular and molecular mechanism of high altitude brain edema. Glial cell foot plate is the blood-brain barrier brain barrier. The important structural components of BBB have been found in recent years in the study of trauma, ischemia, tumorous brain edema, glial cells (and their processes, glial foot) morphological changes before neurons, thought to be the earliest pathological response. However, the changes of glial cell reaction in AMS and HACE have not been reported. Aquaporins are the main molecular basis of water molecule transmembrane movement, and play a key role in regulating brain water balance. It is suggested that AQP4 plays a major role in the pathophysiological process, and the role of AQP4 in the pathogenesis of AMS and HACE is worthy of discussion. The pathological changes of BBB and the expression of AQP4 and its mRNA in glial response were observed under high altitude reaction (AMS) and HACE. And the relationship between them has not been reported yet. In this experiment, we observed the changes of these indexes in 4hs and 4w by using the animal model of 5000m rats at high altitude. To explore the pathogenesis of high altitude reaction / AMS and HACE. The results are as follows: 1. General conditions: the rats in the experimental group showed decreased activity at 72h, obvious congestion in arachnoid, lung and gastrointestinal tract, and increased activity, food intake and hyperemia to nearly normal level. 2. Light microscope observation: the experimental group had slight hyperemia in arachnoid at 24 h and 72 h, and glial cell proliferation and glial nodule formation in the brain tissue after 4 weeks of widening the space around the microvessel.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363

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