MyD88调控TLR2/TLR4二聚体形成的精确位点解析及其干预对ICH的治疗效果

炎症反应在脑出血（ICH）继发性损伤中发挥着重要作用，因此从产生炎症反应的起始关键环节进行干预有望为ICH治疗提供新方法。我们在国家自然基金的资助下，发现ICH后TLR2/TLR4形成的异源二聚体激发的炎症反应在ICH继发性损伤中具有重要作用，同时还发现该二聚体形成依赖于MyD88。因此，我们设想如果能解析MyD88调控TLR2/TLR4二聚体形成的精确位点并针对性干预，可为ICH的治疗提供新方法。我们后续的预实验从传统中药提取的单体SsnB能明显抑制二聚体的形成。因此，本项目拟在现有基础上，利用生物信息学分析方法，结合基因定点突变、基因转染等方法解析MyD88调控TLR2/TLR4二聚体结合的精确位点，采用离体及在体ICH模型，探讨SsnB干预二聚体形成的机制及其对ICH的治疗效果。本项目不仅可深入揭示ICH炎症损伤的关键机制，而且为ICH治疗提供新方法，具有重要理论意义和临床应用前景。

Inflammatory reaction plays an important role in the secondary brain injury after intracerebral hemorrhage (ICH), and we could intervene if we understand the mechanism of the initial inflammatory reaction. Supported by the national nature science foundation of China, we found that the TLR2/TLR4 heterodimer plays a vital role in inflammation reaction after ICH. The formation of TLR2/TLR4 heterodimer depends on MyD88 regulation. We assume that if we analysis the interactive site of MyD88 and TLR2/TLR4 heterodimer, then we could find a potential treatment target for ICH. Our preliminary experiment revealed that SsnB extracted from traditional Chinese herb could inhibit the TLR2/TLR4 heterodimer formation. Therefore, in this study, our aims are to analysis the interactive site of MyD88 and TLR2/TLR4 heterodimer using the methods such as bioinformatics analysis software, gene site-directed mutation and gene transfection. Then we will test the protection of SsnB and clarify its mechanism using in vitro and in vivo ICH models. The results will not only reveal the mechanism of ICH-induced inflammatory injury, but also provide new targets for ICH treatment. This study might have important significance in medical theory and clinical treatment.