猪辅助性带胰头及十二指肠肝肠联合移植的研究

目的介绍猪辅助性带胰头及十二指肠的肝肠联合移植(LSBT)模型技术及其免疫抑制治疗。方法40头杂交长白猪分为两组,每组20头,组内进行辅助性带胰头及十二指肠的LSBT10次。其中A组未用免疫抑制剂治疗,B组采用环孢素A和甲基强的松龙治疗。结果A组动物术后成活时间为(10.33±1.93)d(7~25d),B组全部动物成活超过30d。在没有应用体外转流的情况下,可以耐受血液动力学的波动,血液动力学指标(B组)可以在血流再通后2h恢复正常。B组猪术后血液、尿液和腹腔引流液中的淀粉酶一过性升高,但在1周后回落到术前水平,活检没有发现严重胰腺炎。结论猪辅助性带胰头和十二指肠的LSBT是一种可行的、安全的移植模型,这一模型可以简化传统肝肠移植的技术,应用环孢素A和甲强龙可以有效的抑制猪肝肠移植后急性排斥反应。国家自然科学基金资助项目(39070828

Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction

Tight junctions (TJs) are specialized membrane microdomains of plasma membrane and play an important role in barrier function. IFN-gamma and TNF-alpha have been implicated in intestinal barrier dysfunction. In the present study, we analyzed the effect of IFN-gamma and TNF-alpha on epithelial barrier function and determined the contribution of apoptosis to this process using T84 cells, a model intestinal epithelial cell line. We found that TNF-alpha and IFN-gamma synergistically affected the epithelial barrier and disrupted the structure of TJs. We demonstrated for the first time that treatment with TNF-alpha and IFN-gamma changed lipid composition and fatty acyl substitutions of phospholipids in membrane microdomains of TJs. Alterations of lipid environment affected TJs barrier function and partly removed flotillin-1 and displaced occludin from membrane microdomains of TJs to detergent-soluble fractions. The distribution of claudin isoforms was unaffected by TNF-alpha and IFN-gamma treatment. These findings indicated the interaction between inflammatory cytokines and alterations of lipid composition in membrane microdomains of TJs in the inflammatory processes. The apoptosis inhibitor did not prevent cytokine-induced decrease in TER and increase in permeability to FITC-dextran. Our results suggest that the cytokines directly influence TJ function and modulate both the membrane microdomain localization of TJ proteins and lipid composition of TJs. The effects of proinflammatory cytokines on TJ structure and function provide a mechanism in the pathophysiology of Crohn's disease (CD). Understanding the intracellular mechanisms involved could be important in devising future therapeutic strategies to induce retightening of the leaky TJ barrier. (C) 2007 Elsevier Inc. All rights reserved

营养不良大鼠血浆小分子物质代谢组学的研究

目的：利用代谢组学方法检测能反应营养不良大鼠血浆小分子代谢物质，探讨代谢组学在营养不良研究中的应用。方法：实验分为营养不良组和对照组。对照组大鼠自由进食、饮水，营养不良组自由进水，每天给予该体质量大鼠所需食物的60％。造模成功后，收集大鼠血浆，用液质分析（LC—MS）方法检测并比较两组大鼠血浆小分子物质。结果：营养不良组大鼠与对照组相比，血浆中肉毒碱和色氨酸碎片含量增加，而甜菜碱、棕榈酰肉碱、亚麻酸、二十二碳六烯酸和花生四烯酸等含量均降低。结论：用LC—MS方法检测得到的小分子物质与大鼠营养不良相关。代谢组学可作为营养不良指标的筛选方法