α-黑素细胞刺激素对人外周血T淋巴细胞增殖的抑制作用及其机制初探

发布时间：2018-03-12 18:36

本文选题：α-黑素细胞刺激素　切入点：T淋巴细胞　出处：《第二军医大学》2006年硕士论文　论文类型：学位论文

【摘要】：α-黑素细胞刺激素(α-Melanocyte-stimulating hormone,α-MSH)是一种由13个氨基酸构成的神经肽,由阿黑皮素原(proopiomelanocortin,POMC)经特异蛋白酶裂解而形成,在脑、腺垂体、皮肤及炎症局部等部位有较高的分布。α-MSH具有退热、抗炎、抑制摄食、保护细胞抗紫外线损伤和免疫调节等作用。α-MSH能结合五种型别的黑皮质素受体,这些受体在机体广泛分布,其中包括胸腺、单核/巨噬细胞、中性粒细胞、B细胞、内皮细胞等免疫器官和免疫细胞。α-MSH对实验性自身免疫性疾病、移植排斥反应、实验性致死性内毒素血症、急性呼吸窘迫综合征等多种炎症性疾病的实验动物有显著保护作用。至今未发现其有蓄积毒性,显示出具有广阔的应用前景。 T淋巴细胞在介导细胞免疫应答和辅助体液免疫应答中起着关键作用。已有实验表明,α-MSH对T细胞介导的一些自身免疫性疾病和移植排斥反应均起着有益的调节作用。因此,我们推测α-MSH能直接调节T细胞的功能。本实验室以往的工作已经发现在人永生性T淋巴细胞株Jurkat细胞上存在能与α-MSH特异性结合的受体,并且可以抑制植物凝血素(PHA)刺激引起的Jurkat细胞增殖反应。在此基础上,本课题研究了α-MSH对PHA活化的人外周血T淋巴细胞是否也有增殖抑制作用,并且对其作用机制进行了初步探讨。首先我们证实了α-MSH对体外培养的PHA刺激的健康人外周血T淋巴细胞增殖有明显的抑制作用,当α-MSH的终浓度为1×10~(-7)mol/L时抑制作用最强。为了阐明α-MSH对PHA刺激T细胞增殖的抑制作用机制,我们用流式细胞仪进行了细胞周期分析。结果发现,与仅用PHA刺激的对照组相比,α-MSH+PHA作用后,人外周血T细胞G1期比例明显增多,相同浓度的α-MSH类似物NDP-MSH也具有同样的作用,但抑制作用稍强于α-MSH,提示细胞周期阻滞发生在G1期。通过PI标记,我们进一步利用流式细胞仪分析了α-MSH对PHA刺激的T淋巴细胞晚期凋亡的影
[Abstract]:伪 -Melanocyte-stimulating hormone (伪 -MSHH) is a 13-amino acid neuropeptide formed by the cleavage of proopiomanocortin POMCMC by specific protease. 伪 -MSH is highly distributed in the brain, pituitary gland, skin and inflammatory region, etc. 伪 -MSH has antipyretic and anti-inflammatory properties. 伪 -MSH binds to five types of melanin receptors, including thymus, mononuclear / macrophages, neutrophil B cells, and so on. Endothelial cells and other immune organs and immune cells. 伪 -MSH in experimental autoimmune diseases, transplant rejection, experimental fatal endotoxemia, Experimental animals with acute respiratory distress syndrome and many other inflammatory diseases have significant protective effects, but no accumulative toxicity has been found, which shows that it has a broad application prospect. T lymphocytes play a key role in mediating cellular and humoral immune responses. It has been shown that 伪 -MSH plays a beneficial role in the regulation of T cell-mediated autoimmune diseases and transplant rejection. We speculate that 伪 -MSH can directly regulate the function of T cells. Our previous work has found that there are receptors specifically binding to 伪 -MSH in human immortalized T lymphocyte line Jurkat cells. On the basis of this, we studied whether 伪 -MSH could also inhibit the proliferation of human peripheral blood T lymphocytes activated by PHA. The mechanism of its action is also discussed. Firstly, we confirmed that 伪 -MSH could inhibit the proliferation of peripheral blood T lymphocytes stimulated by PHA in vitro. The inhibitory effect of 伪 -MSH was strongest when the final concentration of 伪 -MSH was 1 脳 10 ~ (-7) mol 路L ~ (-1). In order to elucidate the mechanism of 伪 -MSH 's inhibitory effect on the proliferation of T cells stimulated by PHA, cell cycle analysis was carried out by flow cytometry. Compared with the control group stimulated by PHA alone, the ratio of G 1 phase of T cells in human peripheral blood increased significantly after the treatment of 伪 -MSH PHA, and the same concentration of 伪 -MSH analogues NDP-MSH had the same effect. However, the inhibitory effect of 伪 -MSH was slightly stronger than that of 伪 -MSH, suggesting that cell cycle arrest occurred in G1 phase. By means of Pi labeling, we further analyzed the effect of 伪 -MSH on late apoptosis of PHA stimulated T lymphocytes by flow cytometry.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392

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