淋巴细胞钾通道在应激引起的神经免疫调节变化中的作用

发布时间：2018-04-02 09:55

本文选题：钾通道　切入点：调节性细胞体积减小(RVD)　出处：《吉林大学》2005年博士论文

【摘要】：应激状态下,神经内分泌系统,可通过各种神经递质、内分泌激素、阿片肽等与淋巴细胞上相应的受体结合,调节免疫功能。免疫系统在病毒等外来因素刺激下,也可以分泌多种神经内分泌激素样活性物质发挥免疫作用。已知免疫活性细胞的激活与其细胞膜上的钾通道密切相关。本研究应用小鼠脑缺血缺氧性应激及束缚应激模型,研究不同应激状态下神经免疫系统的变化,以及钾通道介导免疫功能抑制的机制。通过体内体外实验表明:脑缺血缺氧性应激及束缚应激时淋巴细胞的转化受抑制,同时T 淋巴细胞的钾通道Kv1.3 表达下调;氢化可的松及钾通道抑制剂奎宁可以抑制Jurkat 细胞的增殖及RVD 而去甲肾上腺素不能抑制Jurkat 细胞的RVD;应激动物的血清可以抑制Jurkat细胞的增殖,同时对Jurkat 细胞RVD 的抑制作用具有剂量和时间效应关系;但并不是所有应激动物血清组分都对Jurkat 细胞有抑制作用,只有相对分子量大于30KD 的组分才能抑制Jurkat 细胞的RVD。结论:本工作首次发现无论是损伤性应激还是非损伤性应激,均可抑制免疫系统的功能,其机制与T 淋巴细胞上的K+通道表达下调有关;钾通道参与了氢化可的松及免疫抑制因子(应激血清中相对分子量大于30KD 的组分)对细胞免疫功能的抑制作用,其机制可能为钾通道被抑制后,使K+外流减少,阻碍了Ca2+进一步进入细胞内,结果使细胞活化受阻,而去甲肾上腺素对免疫功能的抑制与钾通道无关;推测钾通道是在不同的水平抑制T 淋巴细胞的免疫功能。这将成为临床治疗免疫抑制疾病的一个新的靶点。
[Abstract]:Under stress, the neuroendocrine system can regulate immune function through the binding of various neurotransmitters, endocrine hormones, opioid peptides and corresponding receptors on lymphocytes. The immune system is stimulated by foreign factors such as viruses. It is known that the activation of immunoreactive cells is closely related to the potassium channels on their cell membranes. In this study, the mouse models of hypoxic stress and restraint stress after cerebral ischemia were used. To study the changes of neuroimmune system in different stress states and the mechanism of potassium channel mediated immunosuppression. In vitro and in vivo experiments showed that the transformation of lymphocytes was inhibited under hypoxic stress and restraint stress, and the expression of potassium channel Kv1.3 in T lymphocytes was down-regulated. Hydrocortisone and potassium channel inhibitor quinine could inhibit the proliferation of Jurkat cells and RVD, but norepinephrine could not inhibit the proliferation of Jurkat cells, and the serum of stressed animals could inhibit the proliferation of Jurkat cells. At the same time, the inhibitory effect of RVD on Jurkat cells was dose-dependent and time-dependent, but not all the serum components of stress animals had inhibitory effects on Jurkat cells. Only those components with relative molecular weight greater than 30KD could inhibit Jurkat cells. Conclusion: it is the first time that both traumatic and non-invasive stress can inhibit the function of immune system, and its mechanism is related to the down-regulation of K channel expression on T lymphocytes. Potassium channel is involved in the inhibition of cell immune function by hydrocortisone and immunosuppressive factor (the relative molecular weight of stress serum is greater than 30KD). The mechanism may be that K outflow decreases after potassium channel is inhibited. The further entry of Ca2 into the cells blocked the activation of the cells, but the inhibition of immune function by norepinephrine was independent of potassium channels. It is speculated that potassium channel inhibits the immune function of T lymphocytes at different levels, which will become a new target for clinical treatment of immunosuppressive diseases.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

【共引文献】