胎儿未成熟肺暴露于宫内炎性环境中，是导致早产儿发生支气管肺发育不良(BPD)的重要危险因素，解析BPD炎症反应机制是研究其病理以及治疗的关键点。细胞焦亡是一种新的细胞程序性死亡方式，依赖于Caspase-1并伴有IL-1ß等炎症因子的释放，过度细胞焦亡会诱发多种自身炎症性疾病。我们前期发现，天然药物单体墨旱莲不仅显著改善BPD疾病模型的病理，而且抑制LPS诱导的细胞焦亡。进一步用全转录组测序技术，在LPS诱导的巨噬细胞培养模型中，筛选到一个墨旱莲抑制细胞焦亡的可能作用靶点—Pyrin蛋白。在此基础上，本课题综合应用CRISPR/Cas9基因编辑、基因过表达、shRNA和免疫共沉淀等手段，多角度阐明墨旱莲通过Pyrin抑制细胞焦亡，从而改善BPD的病理机制，明确墨旱莲是否改变了Pyrin结构域的结合能力，并试图明晰Pyrin在细胞焦亡中扮演的角色。本课题的实施将为BPD的防治提供一种新策略。

Bronchopulmonary dysplasia (BPD) is characterized by premature alveolar developmental arrest. Antenatal exposure to inflammation inhibits lung morphogenesis, thus increasing the risk of developing BPD. Pyroptosis is critical innate immune responses via caspase-1-dependent processing and secretion of interleukin 1β (IL–1β), which in turn induces the expression of many other pro-inflammatory cytokines and exaggerates inflammation. Our previous studies have demonstrated natural drug Eclipta prostrata L. improves alveolar development in antenatal LPS-treated rats. We have also shown that Eclipta prostrata L. inhibits LPS-induced caspase-1 activation and decreases IL–1β release in raw264.7 cells. We further identify pyrin may be a critical target of Eclipta prostrata L using the RNA-sequence technology screens. Pyrin has emerged as key regulator of inflammasomes. We thus examine the involvement of pyrin in the inhibition of pyroptosis by Eclipta prostrata L. In this study, we attempt to address whether Eclipta prostrata L. inhibits the pyroptosis through pyrin, and leads to improve alveolar development. Furthermore, we investigate whether Eclipta prostrata L. influences the interaction of pyrin with ASC or caspase-1, and hence regulates caspase-1 activation and consequently IL–1β production. In summary, our results establish a new molecular mechanism pertaining to disrupted lung morphogenesis following intrauterine inflammation, and may provide a new therapeutic drug for BPD treatment.