本文關(guān)鍵詞：α干擾素對(duì)HPA軸的調(diào)節(jié)作用和受體機(jī)制　出處：《青島大學(xué)》2006年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： α干擾素 CRH ACTH 皮質(zhì)酮 阿片受體 α干擾素受體

【摘要】：α干擾素不僅是一種免疫調(diào)節(jié)因子,而且還對(duì)神經(jīng)內(nèi)分泌系統(tǒng)有重要的調(diào)節(jié)作用。其中HPA軸是其作用的靶點(diǎn)之一�，F(xiàn)已證實(shí),α干擾素通過作用于HPA軸各層次而調(diào)節(jié)激素的分泌,但目前資料尚有不同見解。此外,α干擾素調(diào)節(jié)HPA軸的受體機(jī)制迄今也未闡明。本工作利用α干擾素兩種突變體(129Ser-IFNα和38Leu-IFNα)探討α干擾素對(duì)HPA軸調(diào)節(jié)作用的結(jié)構(gòu)基礎(chǔ)和受體機(jī)制,以闡明α干擾素的多功能位點(diǎn)和多受體作用機(jī)制。采用PCR方法對(duì)α干擾素基因定點(diǎn)突變、表達(dá)和純化,獲得了沒有抗病毒活性而有阿片樣鎮(zhèn)痛活性的129Ser-α干擾素和有抗病毒活性而沒有阿片樣鎮(zhèn)痛活性的38Leu-α干擾素α干擾素的兩種突變體。采用大鼠側(cè)腦室埋管給藥的方法給予野生型α干擾素及其兩種突變體和阿片受體拮抗劑納絡(luò)酮,然后利用放射免疫方法測(cè)定全血中CRH、ACTH與皮質(zhì)酮濃度變化和大鼠下丘腦ACTH變化。體外建立原代大鼠下丘腦神經(jīng)原細(xì)胞、垂體AtT20細(xì)胞和原代大鼠腎上腺皮質(zhì)切片,并與野生型α干擾素及其兩種突變體和阿片受體拮抗劑納絡(luò)酮共同孵育后,分別測(cè)定其培養(yǎng)液中CRH、ACTH和皮質(zhì)酮的濃度的變化。結(jié)果表明,野生型α干擾素和具有阿片樣鎮(zhèn)痛活性的129Ser-α干擾素與作為陽(yáng)性對(duì)照的阿片受體激動(dòng)劑嗎啡均可顯著調(diào)節(jié)HPA軸分泌功能,而且該作用可被阿片受體拮抗劑納絡(luò)酮所拮抗。同時(shí)發(fā)現(xiàn),有抗病毒活性但沒有阿片樣鎮(zhèn)痛活性的38Leu-α干擾素對(duì)HPA軸亦有調(diào)節(jié)作用,但其作用相對(duì)較弱,且不受阿片受體拮抗劑納絡(luò)酮的影響。該工作證實(shí),α干擾素對(duì)HPA軸存在重要的調(diào)節(jié)作用,這一作用可能是通過
[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

【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R392

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本文編號(hào)：1391583