细菌内毒素导致的天然免疫失衡与凝血障碍的关联研究

Association between coagulation disorder and bacterial endotoxin-induced innate immunity imbalance

目的探讨天然免疫与凝血相关分子的关系及其理论和其临床意义。方法采用细菌内毒素(LPS)高、低2个剂量分别注射C57BL/6正常小鼠和MyD88基因敲除小鼠,并对正常小鼠注射IL-6、IFN-γ细胞因子抗体,观察小鼠生存率,收获肝组织提取mRNA,RT-PCR的方式检测各相关细胞因子及凝血因子的表达;采用原位孵育实验检测PT(prothrombinase)/PA(plasminogen activator)/PC(protein C)活性;采用Western blot方法检测纤维蛋白沉积,将所有的实验结果使用医学统计软件进行作图分析。结果 IL-6、IFN-γ2种细胞因子抗体通过激活PA活性抑制过量纤维蛋白的生成,延长小鼠存活时间(P<0.003)。结论通过调节天然免疫相关因子的表达来调控凝血系统的功能,控制纤维蛋白适量生成,为治疗败血症提供数据支持。

Innate immune response is the first defense against pathogens. In recent studies, coagulation factors were found to be involved in the whole process of innate immunity, which also been looked as one part of innate immunity. In this study, we aimed to explore the association between innate immune and coagulation factors. Different doses of lipopolysaccharide were used to inject C57BL/6 wild-type mice/MyD88KO mice and the survival was monitor. Iiver was harvested in different time course to test prothrombinase （PT）/plasminogen activator （PA）/ protein C （PC） activities, meanwhile the expression levels of cytokines and coagulation factors, and also the fibrin deposition, then normalized with PRISM analysis software to depict signatures for future use. By comparing all the signatures, we found that anti-IL-6 and anti-INF-＇~ antibodies can regulate fibrin deposition through impacting PA activity. This result will help us to find a promising method to treat disseminated intravascular coagulation （DIC） during sepsis, and to keep appropriate levels of fibrin to confer protection, and mitigate pathology of mass fibrin deposition.