依纳西普抑制脂多糖所致流产的实验研究

Mechanism by which Etanercept inhibits LPS-induced embryo loss

人类和高等动物的免疫系统通过Toll样受体(Toll-like receptor,TLR)识别并清除侵入机体的致病原。其中TLR4识别细菌脂多糖(LPS)。本研究发现,给小鼠腹腔注射LPS可显著增高孕鼠胚胎丢失率。在一定剂量范围内,胚胎丢失率随着LPS剂量的增大而增高。而注射依纳西普(5mg/kg体重)可显著削弱由LPS所引起的小鼠胚胎丢失率增高效应(从30.6%下降至6.0%;P<0.01)。流式细胞术检测发现,依纳西普可显著降低由LPS所引起的小鼠蜕膜F4/80+TNF-α+细胞百分率增高(从26.4%下降至4.7%;P<0.01)。相反,LPS单独处理或LPS与依纳西普先后处理组IL-10+细胞百分率均无显著改变。这些结果提示,依纳西普可通过抑制蜕膜F4/80+TNF-α+细胞而对LPS所诱发的流产起到预防作用。

It is known that Toll-like receptor 4 （TLR4） specifically interacts with LPS and mediates immune response against bacteria. In the current study, it was found that the percentage of embryo loss was significantly boosted in response to lipopo- lysaccharide （LPS） induction in a dose-dependent manner. In addition, ip injection of Etanercept at a dose of 5 mg/kg body weight almost completely abrogated the effect of LPS on murine embryo loss （30.6% vs 6.0% ; P〈0. 01）. In flow cytometry, LPS-induced increase in the proportion F4/80＋ TNF-α＋ cells in F4/80＋ cell population was abolished by Etanercept administra- tion at the indicated dosage （26.4% vs 4.7 % ; P〈0. 01）. In comparison, no significant change was observed in the proportion of F4/80＋ IL-10＋ cells in F4/80＋ cell population among control PBS group, LPS-treated group and the group treated with LPS and Etanereept. The findings indicate that Etanercept may prevent LPS-induced abortion by inhibition on F4/80＋ TNF-α＋ cells.