移植肝免疫损伤过程中肠道微生态的失衡机制及干预研究

肝脏冷、热缺血再灌注是移植肝获取和植入必然经历的过程。其相关的免疫损伤是导致移植肝失功的主要原因之一。国内外报道及本项目组前期研究发现肠道微生态与肝脏病理生理及免疫反应存在密切关系。本项目基于小鼠肝移植模型，围绕肝移植术后免疫损伤过程中肠道微生态失衡及其对肝移植后免疫过程的相互影响这一科学问题，应用DGGE指纹谱、液相质谱（LC-MS）、蛋白免疫印迹、凝胶电泳迁移率和定量PCR技术等实验技术手段，确定肝移植对肠道微生态失衡及肠道屏障功能影响并揭示其机制，探讨不同微生态制剂（抗生素、益生菌制剂、拉克替醇）干预下移植肝病理和代谢的变化规律，阐明肝移植过程中肝脏免疫反应与肠道微生态的相互作用及调控，明确上述生理病理过程及干预方法下整体代谢谱变化及其机制。研究成果可丰富肝移植后肠道微生态与免疫损伤相互影响与调控的生物学理论，并为个体化免疫调控方案提供理论依据和技术支撑。

Episodes of warm and cold ischemia reperfusion injury to liver were essential procedures for harvesting and implanting organs. Immune injury caused by liver ischemia reperfusion attack was a leading cause to liver graft dysfunction. Of note, a series of researches revealed a close relationship between intestine microecology and hepatic immune response. We will focus on the scientific issue of intestine microecology imbalance response to immune injury after liver transplantation and associated impacts on post-transplantation immunosuppression. Liver transplantation and ischemia-reperfusion injury model of mouse will be our choice to conduct this study. DGGE fingerprint spectra, liquid mass spectrometry (LC-MS), protein immune imprinting, transfer rate of gel electrophoresis and quantitative polymerase chain reaction (PCR) technology will be available for us to determine quantitative and qualitative changes in intestine microecology associated with barrier function influence of gut after immune injury to liver graft. We will also discuss the characteristic pharmacokinetics of immunosuppressive agents under the intervention of different Microecologics (Antibiotics, Probiotic-preparation and Lactitol), clarify the question of interactions or regulations between intestine microecology and hepatic immune response after an ischemia reperfusion injury to liver, thus a clear understanding of pathophysiological process and mechanisms of metabolic spectrum change under intervention ensues. Furthermore, for the sake of providing theoretical and technical support, our work could enrich the biological theory referred to the interactions or regulations of intestine microecology and post-transplantation immunosuppressive therapy.