重组人白细胞介素1受体拮抗剂治疗重症肝炎的药效学研究

重症肝炎，又称为急性肝衰，其临床表现特点是发病急，病程短，预后差，死亡率高(60%-70%)。在我国，重症肝炎的病因主要是病毒性肝炎，约占80%。在对重症肝炎的治疗方面，最佳临床治疗方案是肝移植，除此之外，采用药物、血浆置换和人工肝支持系统等辅助治疗来抑制肝细胞凋亡和促进肝细胞增殖。但到目前为止，尚未找到治疗重症肝炎的有效药物。本实验室通对急性肝衰的前期研究发现白细胞介素1受体拮抗剂（IL-1Ra）对重症肝炎模型动物具有良好的保护作用。结合国内外的研究进展，我们提出IL-1信号通路是重症肝炎的重要治疗靶点，并应用不同重症肝炎动物模型来开展IL-1Ra治疗重症肝炎的的临床前药效学研究，同时研究IL-1Ra通过IL-1R/MyD88信号通路抑制肝细胞凋亡的作用机制。这有助于发现治疗重症肝炎的新型重组蛋白类药物，形成拥有自主知识产权的新药，具有显著的社会效益和意义。

Acute hepatic failure (AHF), called as fulminant hepatic failure, is a severe liver injury which caused multiorgan failure with an extremely high mortality rate (60-70%). the basic etiopathogenic agent of AHF was viral hepatitis (80%) in China. Liver transplantation has been shown to be the most effective therapy. The drugs, blood exchange or bio-artificial liver assist devices is used to inhibit hepatocytes apoptosis and improve hepatocytes proliferation,but no effects on patients survival. In the recent, no drugs were found in curing AHF. Our lab has found that interleukin-1 receptor antagonist (IL-1Ra) could protect hepatocyte in AHF model mouse. According to research progress of IL-1Ra function in AHF, We have a hypothesis which IL-1 signal pathway is a target in curing AHF, and start to study preclinical pharmacodynamics of IL-1Ra treating AHF on different models. Another side, we will investigate whether IL-1Ra regulate hepatocytes survival depending on IL-1R-MyD88 pathway in AHF. This research should be helpful to find new recombinant protein drug whose intellectual property will be owned. There is big value to society in our country.