幼年心理应激对支气管哮喘大鼠中枢与外周免疫功能的影响

发布时间：2018-05-10 12:54

本文选题：支气管哮喘 + 心理应激　；参考：《山东大学》2010年硕士论文

【摘要】： 目的本研究采用卵蛋白(OVA)致敏和束缚应激的方法建立心理应激与支气管哮喘大鼠模型,旨在：(1)考察心理应激对哮喘大鼠中枢和外周免疫功能的影响；(2)观察不同年龄阶段(成年和幼年)心理应激对哮喘大鼠气道炎症和免疫功能的影响；(3)探讨幼年和成年心理应激影响哮喘的潜在生理机制及HPA轴在这一过程中的作用。方法选用21日龄(断奶)健康雄性Wistar幼年大鼠32只,随机分为正常对照组、哮喘模型组、成年心理应激哮喘组(成年应激组)和幼年心理应激哮喘组(幼年应激组),每组8只。建立心理应激与哮喘动物模型,观察动物行为学与肺组织形态学变化,苏木精-伊红(HE)染色与白细胞亚群计数,放免法测定血清IL-4、皮质醇、肺泡灌洗液(BALF)免疫球蛋白(Ig)E及脑组织IL-1β含量。结果1.卵蛋白激发后第7天正常对照组大鼠无明显异常,哮喘模型组大鼠出现烦躁不安,喷嚏,抓咬,呼吸气促,腹肌收缩加深等表现,严重者呼吸减慢或节律不齐,轻度紫绀,四肢瘫软,行动迟滞或俯伏不动,反应迟钝；激发后第14天发现大鼠体重减轻、毛色失去光泽,反应迟钝。成年应激组和幼年应激组动物上述表现更为显著,且具有拒捕、抓咬、不安、狂躁和惊恐、依从两种不同的行为特点。 2.正常对照组大鼠肺组织无明显炎性病变；哮喘模型组气道上皮排列不整,支气管腔狭窄,粘膜损伤,并有嗜酸性粒细胞、淋巴细胞及单核细胞浸润；成年应激组和幼年应激组大鼠气道上皮排列不整明显,肺间质有大量炎性细胞浸润,气道及血管周围炎性细胞明显增多,炎性病变更为严重。哮喘模型组、成年应激组和幼年应激组大鼠白细胞总数和嗜酸性粒细胞数目均显著高于正常对照组(p0.01),成年应激组嗜酸性粒细胞数显著高于哮喘模型组(p0.05),幼年应激组白细胞和嗜酸性粒细胞数均显著高于哮喘模型组(p0.05)。 3.哮喘模型组、成年应激组和幼年应激组大鼠血清IL-4含量均显著高于正常对照组(p0.05),成年应激组和幼年应激组大鼠血清IL-4含量显著高于哮喘模型组(p0.05)。哮喘模型组、成年应激组皮质醇含量显著高于正常对照组(p0.01),幼年应激组显著低于正常对照组(p0.05)。成年应激组皮质醇含量显著高于哮喘模型组(p0.05)。 4.各组大鼠BALF中IgE含量差异无统计学意义(p0.05)。 5.哮喘模型组和成年应激组大鼠脑组织IL-1β含量显著高于正常对照组(p0.05),幼年应激组显著低于哮喘模型组(p0.05)。结论1.心理应激加重大鼠免疫功能的紊乱,加重大鼠哮喘。具体表现为：束缚应激加重哮喘大鼠支气管和肺组织局部炎性病变,导致局部白细胞总数、嗜酸性粒细胞数目增加及行为和多项免疫指标的改变。 2.幼年束缚应激导致血清皮质醇和中枢IL-1β含量降低,而成年束缚应激引起哮喘动物血清皮质醇和中枢IL-1β含量的升高。 3.心理应激引起神经-内分泌-免疫系统交互作用方式的改变,HPA轴在这一过程中具有重要作用。幼年和成年应激均加重哮喘症状,但幼年心理应激加重哮喘的机制却不同于成年心理应激：成年束缚应激活化HPA轴的功能,对外部威胁作出适应性反应,幼年心理应激则对HPA轴的应答性具有长效抑制效应。应激年龄是心理应激作用性质和方向的一个重要影响因素。
[Abstract]:Objective the aim of this study was to establish a rat model of psychological stress and bronchial asthma by using ovalbumin (OVA) sensitization and restraint stress. (1) to investigate the effects of psychological stress on the central and peripheral immune function of asthmatic rats; (2) to observe the airway inflammation and immune function of asthmatic rats at different age stages (adult and young years). (3) to explore the potential physiological mechanism of juvenile and adult psychological stress affecting asthma and the role of HPA axis in this process.
Methods 32 healthy male Wistar rats of 21 days of age (weaning) were randomly divided into normal control group, asthma model group, adult psychological stress asthma group (adult stress group) and juvenile psychological stress asthma group (juvenile stress group), 8 rats in each group. The model of psychological stress and asthma was established, and the changes of animal behavior and lung histomorphology were observed. Hematoxylin eosin (HE) staining and leukocyte subgroup count, radioimmunoassay were used to determine serum IL-4, cortisol, alveolar lavage fluid (BALF) immunoglobulin (Ig) E and the content of IL-1 beta in brain tissue.
Results there was no obvious abnormality in the normal control group on the seventh day after 1. ovalbumin stimulation. The rats in the model group of asthma appeared to be restless, sneezing, grasping, breathing, and deepening the contraction of the abdominal muscles. The severe breathing slowed or the rhythm was inhomogeneous, mild cyanosis, limp limbs, delayed action or slow reaction, and delayed reaction; fourteenth days after stimulation, the rats were found big. Rats lose weight, hair color loses luster, and reaction is slow. Adult stress group and young stress group have more remarkable performance, and have two different behavior characteristics, such as rejection, bite, restlessness, manic and panic.
2. in the normal control group, there was no obvious inflammatory lesion in the lung tissue of the normal control group. The airway epithelium in the model group was not arranged, the bronchial tube was narrow, the mucous membrane was damaged, and the eosinophils, lymphocytes and mononuclear cells infiltrated, and the airway epithelium of the adult stress group and the young stress group was unarranged, and the interstitial lung was infiltrated by a large number of inflammatory cells. The number of leukocytes and the number of eosinophils in the asthmatic group, the adult stress group and the young stress group were significantly higher than that of the normal control group (P0.01). The eosinophil number of adult stress group was significantly higher than that of the asthma model group (P0.05), and the white blood cell in the juvenile stress group was significantly higher than that in the adult stress group. The number of eosinophils was significantly higher than that in asthmatic model group (P0.05).
3. the serum IL-4 content in the adult stress group and the young stress group was significantly higher than that of the normal control group (P0.05). The serum IL-4 content of the adult stress group and the young stress group was significantly higher than that of the asthma model group (P0.05). The cortisol content in the adult stress group was significantly higher than that of the normal control group (P0.01), the young stress group was significantly higher than the normal control group. Significantly lower than normal control group (P0.05). The cortisol content in adult stress group was significantly higher than that in asthma model group (P0.05).
4. there was no significant difference in IgE content in BALF of rats in each group (P0.05).
5. in the asthma model group and adult stress group, the contents of IL-1 beta in the brain tissue of rats were significantly higher than those in the normal control group (P0.05), and the juvenile stress group was significantly lower than that in the asthma model group (P0.05).
Conclusion 1. the psychological stress and the disorder of the immune function of rats aggravates the asthma in rats. The specific manifestation is that the binding stress aggravates the local inflammatory lesions in the bronchial and lung tissues of the asthmatic rats, resulting in the total number of leukocytes, the increase of the number of eosinophils and the changes of the behavior and many immune indexes.
2. juvenile binding stress caused the decrease of serum cortisol and central IL-1 beta, and the increase of serum cortisol and central IL-1 beta in asthmatic animals caused by adult restraint stress.
3. psychological stress causes a change in the interaction of the neuroendocrine immune system, the HPA axis plays an important role in this process. Both young and adult stress aggravate the symptoms of asthma, but the mechanism of juvenile psychological stress aggravates asthma is different from adult psychological stress: adult binding should activate the function of the HPA axis and make an external threat. Adaptive response, young psychological stress has a long-term inhibitory effect on the response of HPA axis. Stress age is an important factor in the nature and direction of psychological stress.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R395.1

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