α干扰素对HPA轴的调节作用和受体机制

发布时间：2018-01-07 07:29

本文关键词：α干扰素对HPA轴的调节作用和受体机制　出处：《青岛大学》2006年硕士论文　论文类型：学位论文

【摘要】：α干扰素不仅是一种免疫调节因子,而且还对神经内分泌系统有重要的调节作用。其中HPA轴是其作用的靶点之一。现已证实,α干扰素通过作用于HPA轴各层次而调节激素的分泌,但目前资料尚有不同见解。此外,α干扰素调节HPA轴的受体机制迄今也未阐明。本工作利用α干扰素两种突变体(129Ser-IFNα和38Leu-IFNα)探讨α干扰素对HPA轴调节作用的结构基础和受体机制,以阐明α干扰素的多功能位点和多受体作用机制。采用PCR方法对α干扰素基因定点突变、表达和纯化,获得了没有抗病毒活性而有阿片样镇痛活性的129Ser-α干扰素和有抗病毒活性而没有阿片样镇痛活性的38Leu-α干扰素α干扰素的两种突变体。采用大鼠侧脑室埋管给药的方法给予野生型α干扰素及其两种突变体和阿片受体拮抗剂纳络酮,然后利用放射免疫方法测定全血中CRH、ACTH与皮质酮浓度变化和大鼠下丘脑ACTH变化。体外建立原代大鼠下丘脑神经原细胞、垂体AtT20细胞和原代大鼠肾上腺皮质切片,并与野生型α干扰素及其两种突变体和阿片受体拮抗剂纳络酮共同孵育后,分别测定其培养液中CRH、ACTH和皮质酮的浓度的变化。结果表明,野生型α干扰素和具有阿片样镇痛活性的129Ser-α干扰素与作为阳性对照的阿片受体激动剂吗啡均可显著调节HPA轴分泌功能,而且该作用可被阿片受体拮抗剂纳络酮所拮抗。同时发现,有抗病毒活性但没有阿片样镇痛活性的38Leu-α干扰素对HPA轴亦有调节作用,但其作用相对较弱,且不受阿片受体拮抗剂纳络酮的影响。该工作证实,α干扰素对HPA轴存在重要的调节作用,这一作用可能是通过
[Abstract]:Interferon is not only an immune regulator, but also has an important role in the regulation of neuroendocrine system. The HPA axis is one of the target function. It has been confirmed that alpha interferon by acting on the HPA axis of each level and the regulation of hormone secretion, but at present there are different data views. In addition, the mechanism of interferon receptor regulation of the HPA axis has not clarified. The use of interferon alpha two mutants (129Ser-IFN alpha and 38Leu-IFN alpha) of alpha interferon regulating effect on HPA axis structure based and receptor mechanism, with multi function and multi site of interferon receptor mechanism. Using PCR method of interferon alpha gene mutation, expression and purification, obtained no antiviral activity of interferon alpha and 129Ser- are opioid analgesic activity and antiviral activity but not opioid analgesic activity of 38Leu- alpha interferon alpha interferon Two mutants. Using rat intracerebroventricular catheter delivery method to wild-type alpha interferon and its two mutants and the opioid receptor antagonist naloxone, and determination of blood CRH by RIA, the change of ACTH and corticosterone concentrations and ACTH in hypothalamus of rats. Primary hypothalamic neurons in primary rat pituitary cells in vitro, AtT20 cells and primary rat adrenal cortex slices, and the wild type of interferon alpha and its two mutants and the opioid receptor antagonist naloxone after CO incubation and determination in the medium were ACTH and CRH respectively, the corticosterone concentration change. The results showed that wild type alpha interferon and with opioid analgesic activity of interferon alpha and 129Ser- as a positive control of the opioid receptor agonist morphine can significantly modulate the secretion function of HPA axis, and the effect could be the opioid receptor antagonist naloxone antagonized at the same time. 38Leu- found that interferon antiviral activity but not opioid analgesic activity can regulate the function of HPA axis, but the effect is relatively weak, and not by the opioid receptor antagonist naloxone. This work confirmed that interferon exists an important role in the regulation of the HPA axis, the effect is through

【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392

【共引文献】