HMGB1在外伤后眼内炎症发生中的作用机制研究

我们前期研究发现外伤性眼内炎动物模型的炎症高峰出现在无菌生长时，提示存在某些把控因子调节晚期炎症，我们提出“具有损伤识别和晚期炎症调节双重作用的HMGB1可能是外伤后眼内炎症反应调控中的关键性因子”的科学假设。拟以外伤性眼内炎症患者和动物模型作为研究主体，利用ELISA、免疫荧光等分子生物学技术，定性、定量分析HMGB1在外伤后眼内炎症发生中的表达规律和作用机制。从检测HMGB1及其配体RAGA、TLR2/4/7在动物外伤性眼内炎发生中的动态表达和与其它炎性细胞因子的关系入手，确定HMGB1参与外伤性眼内炎的发生方式；再通过研究眼外伤患者眼内HMGB1的表达与眼外伤严重程度、眼内炎发生与否、炎症程度、及其与炎性细胞因子之间的关系，确定HMGB1在预测和评估外伤后眼内炎症的生物价值；最后通过阻断实验，进一步确定以HMGB1为靶点干预外伤后眼内炎症的治疗效果和作用机制，为临床转化提供理论支撑。

Our previous study found that there is no bacterial growth during the peak of inflammation in rabbits with traumatic endophthalmitis. It implyed that there may be a key factor which regulates and controls the development of late inflammation. High Mobility Group Box 1(HMGB1) can play roles as damage associated molecular patterns (DAMPs)，chemokine and cytokine, and it is thought to be a therapeutic target for trauma, sterile inflammation and infection. We hypothesize that HMGB1 may be a key factor in the development of trauma induced ocular inflammation. Ocular trauma patients and animal models of traumatic endophthalmitis are involved in this research. ELISA and immunofluorescence techniques are performed to exam the expression of HMGB1 and to analyze the role of HMGB1 in the development of intraocular inflammation after trauma. We plan to investigate the expression of HMGB1 and its ligands, RAGA and TLR2/4/7, in the animal model of traumatic endophthalmitis first. And the relationship between HMGB1 and other proinflammtion cytokines will analyzed. Then we will investigate the levels of HMGB1 and its ligands, RAGA and TLR2/4/7, in patients with ocular trauma and with trauma-induced inflammation and analyze the difference between these patients. Finally, we plan to perform blocking experiments in the animal model of traumatic endophthalmitis in order to investigate the therapeutic role of HMGB1 in traumatic endophthalmitis. Above all, we hope to determine the role and mechanism of HMGB1 in the development of trauma induced ocular inflammation in this study.