海蛇蛇毒中的抗炎活性成分及其作用机理未明。本课题组前期从青环海蛇中获得了一条选择性TNFR1拮抗肽Hydrostatin-SN10，靶点明确，对类风关等疾病具有显著的抗炎活性。然而，Hydrostatin-SN10的分子结构及其抗炎机制尚不明确。本课题拟通过结构生物学方法研究Hydrostatin-SN10与TNFR1复合物晶体结构，明确Hydrostatin-SN10与TNFR1的结合位点、方式，阐明其选择性拮抗TNFR1的分子机制；分析对TNF-α促炎活性及相关信号通路的影响，最终在关节炎动物模型上评价体内抗炎和免疫调控效应。本课题的完成将给选择性TNFR1拮抗肽Hydrostatin-SN10抗炎机理的揭示提供最直接的结构生物学证据，为研发Hydrostatin-SN10成为具有自主知识产权的、靶点明确的海洋生物来源新型选择性TNF-α受体抑制剂多肽药物奠定最坚实的基础。

The anti-inflammatory bioactive components of sea snake venom and its mechanism of action is unknown. We previously obtained a TNFR1-selective antagonist peptide Hydrostatin-SN10 from Hydrophis cyanocinctus, which has significant anti-inflammatory activity in rheumatoid arthritis and related diseases. However, the molecular structure of Hydrostatin-SN10 and its anti-inflammatory mechanism remain unclear. This project aims to study the crystal structure of TNFR1-SN10 complex via structural biological methods, identify the binding sites and interacting properties of Hydrostatin-SN10 with TNFR1, and elucidate its molecular mechanism of selective antagonism towards TNFR1; analyze the effects of the peptide on the pro-inflammatory of TNF-α and associated signaling pathways, and finally evaluate the in vivo anti-inflammatory and immunoregulatory effects of Hydrostatin-SN10 in animal models of arthritis. Our project will provide a direct structural biological evidence to clarify the anti-inflammatory mechanism of TNFR1-selective antagonist peptide Hydrostatin-SN10, and can also lay a solid foundation for Hydrostatin-SN10 to develop into a new class of marine-derived TNFR-inhibitory peptide drugs with proprietary intellectual property rights.