PD-1 对小鼠内毒素血症的保护作用及其机制研究

Protection of PD-1 against LPS-induced endotoxemia and the underlying mechanism

摘要:

目的：革兰阴性细菌感染所致的多器官衰竭/功能障碍综合征仍是目前发达国家和发展中国家儿童死亡的主要原因之一，发病机制尚不明确。本研究探讨了具有负性免疫调节作用的免疫球蛋白超家族的成员程序性死亡受体-1（programmed death-1，PD-1）对革兰阴性细菌的主要致病成分脂多糖（LPS）所致内毒素血症的保护作用及可能的相关机制。方法PD-1+/+和PD-1/小鼠各10只经腹腔注射LPS（10 mg/kg）,观察其 72 h 存活情况；另对PD-1+/+和PD-1/小鼠各40只经腹腔注射LPS（5 mg/kg），分别在注射前（0 h）及注射后1.5、3、6 h 采血，用ELISA检测血浆中多种炎性成分的含量。结果PD-1/小鼠在接受大剂量 LPS注射后，存活率明显低于PD-1+/+小鼠。注射5 mg/kg LPS后，PD-1/小鼠生成的具有促炎作用的介质TNF-α、IL-1β、IL-12及IL-17高于PD-1+/+小鼠。结论 PD-1对LPS所致的内毒素血症具有保护作用，可能是通过调节炎性成分的生成来实现的。［中国当代儿科杂志，2010，12(10)：812-815］

Abstract:

OBJECTIVE: Gram-negative bacteria-induced multiple organ failure/dysfunction syndrome (MOF/MODS) is one of the leading causes of death through the world. The member of immunoglobulin family programmed death-1 (PD-1) is a negative immune regulator. This study investigated the protective effect of PD-1 as well as the underlying mechanism in LPS-induced endotoxemia. METHODS: Ten PD-1+/+ and ten PD-1 knockout (PD-1/) mice were injected peritoneally with LPS (10 mg/kg), and the survival was observed within 72 hrs after LPS injection. The other 40 PD-1+/+ and 40 PD-1/mice were injected peritoneally with LPS (5 mg/kg). Blood samples were collected before injection and 1.5, 3 and 6 hrs after LPS injection (n=10 each time point). Serum levels of various inflammatory mediators were measured using ELISA. RESULTS: The survival rate in PD-1/mice was noticeably lower than that in PD-1+/+ mice after 10 mg/kg LPS injection. Serum levels of inflammatory mediators TNF-α, IL-1β, IL-12 and IL-17 in PD-1/mice were higher than those in PD-1+/+ mice after 5 mg/kg LPS injection. CONCLUSIONS: PD-1 can protect mice from LPS-induced endotoxemia probably through its regulation on inflammatory mediator production.［Chin J Contemp Pediatr, 2010, 12 (10):812-815］