GBS在ROS介导下激发胎膜炎症反应的机理研究

B族链球菌（GBS）定植/感染是导致胎膜早破、早产和新生儿早发型感染的重要原因，临床存在对抗菌素不敏感的问题，但发生机制尚未阐明。我们的前期研究揭示：1.GBS感染母胎血中炎症因子IL-1ß显著升高；2.GBS可诱导胎膜表达TLR-2受体、促进活性氧簇（ROS）形成、增加IL-1ß释放，IL-1ß进一步致胎膜细胞焦亡（pyroptosis）；3.抗氧化剂NAC及NADPH氧化酶（NOX）抑制剂DPI能抑制ROS形成及IL-1ß释放。我们认为GBS病原相关分子模式PAMPs（β-HL, PGPS, LTA）与活性GBS同样重要，GBS/PAMPs在ROS介导下可能直接激活炎性小体和NF-ҡB通路，而抑制NF-ҡB和ROS相关的NOX活性将有效阻遏GBS/PAMPs激发的胎膜炎症反应。我们将利用胎膜外植体及羊膜细胞，围绕以上假设展开研究，旨在独辟蹊径寻找潜在治疗方案，减少GBS相关母婴并发症。

Groups B Streptococcus (GBS) colonization/infection is an important cause of prelabor rupture of membranes, spontaneous preterm birth and early-onset neonatal infections. In clinical practice, there are conditions of resistance and insensitivity of antibiotic treatment to GBS. The exact mechanism has not been elucidated yet. Our previous studies revealed that: (1) The concentrations of IL-1ß in maternal and fetal blood were significantly increased in GBS positive group comparing with those in GBS negative group; (2) In fetal membranes, GBS could induce the expression of TLR-2 receptor, promote the production of reactive oxygen species (ROS) and increase the release of IL-1ß. Moreover, IL-1ß could enhance pyroptosis, a kind of cell death induced by inflammasome, in fetal membranes; (3) Antioxidant NAC and NADPH oxidase (NOX) inhibitor DPI can significantly inhibit ROS production and IL-1 ß release. We think that: (1) GBS related pathogen-associated molecular patterns(PAMPs: β-hemolysin, PGPS, LTA ) are as important as active GBS in inducing the inflammation of fetal membranes; (2) GBS/GBS-related PAMPs activate inflammasome as well as NF-ҡB via ROS; (3) Inhibition of NF-ҡB activity and ROS-related NOX activity can inhibit the inflammatory response of fetal membranes stimulated by GBS/GBS-related PAMPs. This project will focus on validating the above innovative hypothesis by a series of experiments, based on human fetal membrane organ explant and primary human amnion epithelial cells. We aim to provide insights into potential preventative/treatment strategies and reduce GBS-related maternal and infant complications.