Toll样受体在中药成分保护肠黏膜微血管内皮细胞免受细菌毒素损伤中的作用研究

Toll-like receptors (TLRs), as well as interleukin 1 receptor associated protein kinase (IRAK) and tumor necrosis factor receptor activating factor 6 (TRAF6) that indeced by myeloid differentiation protein-88 play important roles in the inflammatory reaction. This project is aimed to study the effects of bacteria endotoxin and Shiga-like toxin (SLT)on the expression of TLR2 and TLR4,the secretion of MyD88, IRAK and TRAF6 by the intestinal mucosal microvascular endothelial cells(IMMECs) in order to explain the roles of TlRs and their signal pathways of bacterial endotoxin and Shiga-line toxin in inflammaotory reaction.Then,by studying the expression of TLR2 and TLR4, and the secretion of MyD88, IRAK and TRAF6 by the IMMECs which are protected by the ingredients of Chinese herbs, such as matrine, baicalin and meletin, to investigete the roles of toll-like receptors and the signal pathways of IRAK and TRAF6 induced by MyD88 in the process of Chinese herbs to protect IMMECs anginst injuries induced by bacterial endotoxin and Shiga-like toxin. The results of this study will reveal the mechansim of Chinese herbs to anti-both the bacterial endotoxin and Shiga-line toxin, and will provide theoretical basis for the further study on the Chinese herbs with effects to anti bacterial toxin.

Toll样受体及其由髓样分化因子88（MyD88）所介导的白介素-1相关蛋白激酶(IRAK)、肿瘤坏死因子受体活化因子6(TRAF6)信号通路在内毒素诱导的炎症反应中起着重要作用。本项目以体外培养的大鼠肠黏膜微血管内皮细胞为材料，通过研究内毒素和志贺样毒素对肠黏膜微血管内皮细胞TLR2和TLR4及其由Myd88所介导的IRAK和TRAF6信号通路的影响，探讨细菌毒素所引起的炎症反应中toll样受体的作用及其信号传导通路。同时，研究受到中药成分（苦参碱、槲皮素、黄芩苷）保护的肠黏膜微血管内皮细胞对toll样受体TLR2、TLR4表达以及MyD88、IRAK、TRAF6的分泌的影响，探讨toll样受体及由MyD88诱导的IRAK和TRAF6信号通路在中药保护肠黏膜微血管内皮细胞免受细菌毒素损伤中的作用，从而揭示中药成分抗细菌毒素作用的机制，为抗炎中药的进一步研究提供理论依据。

Toll样受体及其由髓样分化因子88（MyD88）所介导的白介素-1相关蛋白激酶(IRAK)、肿瘤坏死因子受体活化因子6(TRAF6)信号通路在炎症反应中起着重要作用。本项目以体外培养的大鼠肠黏膜微血管内皮细胞为材料，研究了受到中药成分槲皮素、黄芩苷保护的肠黏膜微血管内皮细胞对toll样受体TLR2、TLR4以及MyD88、IRAK、TRAF6表达的影响，以探讨toll样受体及由MyD88诱导的IRAK和TRAF6信号通路在槲皮素、黄芩苷保护肠黏膜微血管内皮细胞免受细菌毒素损伤中的作用，从而揭示中药成分槲皮素和黄芩苷抗细菌毒素作用的机制。研究结果发现，Toll样受体4的激活及其介导的MyD88信号通路在细菌内毒素（LPS）致体外培养的大鼠肠黏膜微血管内皮细胞损伤中起重要作用。中药成分黄芩苷和槲皮素能通过抑制LPS致Toll受体介导的MyD88信号通路激活，从而抑制炎性因子的分泌，保护RIMMVECs细胞。同时，Toll样受体2的激活及其介导的MyD88信号通路在细菌外毒素肽聚糖致体外培养的大鼠肠黏膜微血管内皮细胞损伤中起关键作用。中药成分槲皮素能抑制肽聚糖导致的RIMMVECs细胞Toll2受体介导的MyD88信号通路激活，从而降低炎性因子的分泌，抑制细胞炎性反应。总之，Toll样受体及其介导的MyD88信号通路参与并主导了中药成分槲皮素和黄芩苷保护细菌毒素致肠黏膜微血管内皮细胞损伤。