GABA在肝星状细胞免疫抑制特性中的作用及机制研究

已有证据显示，肝脏局部的免疫反应是决定肝纤维化发生发展的关键环节，肝星状细胞是这一免疫反应之中心。活化的肝星状细胞不仅具抗原提呈能力，且可抑制T细胞的活化和增值，即具有免疫抑制特性。GABA是一种重要的抑制性神经递质，它也可抑制T细胞的活化和增值。我们前期研究发现GABAB受体通过抑制肝星状细胞活化而改善实验性大鼠的肝纤维化。由此我们推测，GABA及受体可能是肝星状细胞和T淋巴细胞相互作用的介导者并调控肝星状细胞的免疫抑制特性。本项目拟通过细胞趋化实验、免疫共定位、细胞共培养、基因敲除小鼠、流式细胞术、免疫印迹以及动物模型等实验手段来阐明GABA及其受体在肝星状细胞免疫抑制特性中的调控机制，对深入阐明肝纤维化的分子机制有重要意义，进一步可为抗纤维化的免疫疗法提供新的思路。

Evidences indicated that the immunity microenviroment in liver plays a key role in process of liver fibrosis. The hepatic stellate cell was the center of this enviroment for regulating the inflammatory and fibrotic reaction. The active hepatic stellate cell is not only the antigen-presentating cell but also can inhibit activation and proliferation of T lymphocyte. Recent rearches indicated that GABA can also inhibit the activation of T lymphocyte.γ-Aminobutyric acid B receptor(GABABR) amelioated liver fibrosis through inhibition of hepatic stellate cell's proliferation in our previous study. Based on these evidences, we put forward hypothesis that GABA and GABA receptors may be the mediators for interaction of hepatic stellate cell and T lymphocyte and regulating the property of immunosuppression. We will use some experimental methods including cell chemoattractant,lanser scanning confocal, cell co-culture,gene knock out,flow cytometry,westernblot and animal model to clarify the contribution to the immunosuppression property of hepatic stellate cell and molecular mechanism underlying this regulation in the present study. This research will have an important significance for elucidating the mechanism of liver fibrosis and provide a new thinking for therapy of liver fibrosis through immunity treatment.