基于LPS-TLR4信号通路介导HLA-B27相关前葡萄膜炎易感家族发病机制的基础研究

HLA-B27阳性前葡萄膜炎除具有明显的家族聚集性、症状重、复发率高、合并全身疾病等特点外，还明显表现为家族内个体易感性的差异。目前国内外研究认为葡萄膜炎的发生可能和G-细菌感染后TLR-4介导的炎症信号传导通路激活相关。我们在前期大鼠EIU虹膜巨噬细胞及HLA-B27阳性前葡萄膜炎患者外周血单核细胞均发现TLR-4高表达，并证实TLR4-MyD88-NF-κB传导途径激活在前葡萄膜炎发病中的重要性。为探索同一家族个体间发病的差异性，我们拟通过基因芯片技术对5个HLA-B27相关前葡萄膜炎易感家族(均有HLA-B27阳性未发病及发病缓解期、HLA-B27阴性未发病成员）外周血单核细胞LPS刺激前后基因表达差异的检测,功能分析, siRNA干扰验证，以期揭示HLA-B27阳性前葡萄膜炎位于LPS-TLR4传导通路重要的致病基因，为其功能研究及基因治疗提供理论依据。

HLA-B27 associated anterior uveitis has a significant familial aggregation, sereous symptoms, a high recurrence rate and serous complications.The different susceptivity among the HLA-B27 positive individuals in the same family remains unknown.Study at home and abroad suggest that the HLA-B27 associated anterior uveitis is related to the gram-negative bacterial infection and Toll-like receptor 4-mediated inflammation-related signaling pathways. Our previous work demonstrated high of Toll-4 in the peripheral blood mononuclear cells of HLA-B27 positive acute anterior uveitis patients and iris macrophages of endotoxin-induced uveitis rats, and the importance of activation of TLR4-MyD88-NF-κB pathway in the etiology of anterior uveitis. Through comparing HLA-B27 positive families with acute anterior uveitis peripheral blood mononuclear cells with the normal control group after LPS stimulation by gene chip technology and siRNA intereing, we hope found the key genes in the upstream of LPS-TLR4 signaling pathway, and provide a theoretical basis in gene therapy for the HLA-B27 positive anterior uveitis.