新生儿支气管肺发育不良（BPD）发病率及早期病死率居高不下，孕期环境污染物暴露与其发生密切相关。环境污染物全氟辛烷磺酸（PFOS）因具疏油和疏水特性而被广泛应用。我们前期研究发现，PFOS孕期暴露可致子代大鼠肺部出现BPD的特征性病理改变，但机制未明；同时发现NLRP3表达升高，而后者可诱导细胞焦亡，且细胞焦亡过程伴随大量促炎症因子释放。据此推测PFOS可能通过激活NLRP3炎症小体诱导细胞焦亡而导致BPD。本课题以PFOS激活NLRP3炎症小体为切入点，通过孕期及哺乳期不同时相不同剂量PFOS暴露的在体研究及离体不同时相炎症小体的siRNA和抑制剂干预，采用分子生物学及单细胞测序等技术，揭示孕期和哺乳期PFOS暴露对肺泡上皮细胞发育和成熟阻滞及损伤的作用机制。从环境污染新视角探索PFOS对子代肺发育毒性作用的新机制和新靶点，对BPD早期预防和干预具重要意义，并为政府制定政策提供科学依据。

The incidence and early mortality of neonatal bronchopulmonary dysplasia (BPD) remain high. Environmental pollution exposure during pregnancy is closely related to its occurrence. Perfluorooctane sulfonic acid (PFOS), an environmental pollutant, has been widely used for industry and daily life due to its non-hydrophilic and non-lipophilic properties. Our previous studies have found that PFOS exposure during pregnancy can induce characteristic pathological changes of BPD in the lung of offspring rats, and the mechanism is not clear. At the same time, we found that the expression of NLRP3 increased, while the latter can induce cell pyroptosis, and the process of cell death is accompanied by a large number of pro-inflammatory factors. It is speculated that PFOS may induce BPD by activating NLRP3 inflammasome to induce cell pyroptosis. In this study, the mechanism of PFOS exposure on alveolar epithelial cell development and maturation arrest and injury during pregnancy and lactation will be revealed through in vivo study of PFOS exposure at different doses during pregnancy and lactation and in vitro intervention of siRNA and inhibitors of inflammasome at different phases. Molecular biology and single cell sequencing techniques will be used to reveal the mechanism of PFOS exposure on alveolar epithelial cell development and maturation arrest and injury. The new mechanism and target of PFOS on pulmonary developmental toxicity of offspring proposed in the studies are from a new point of view of environmental pollution, which is of great significance for early prevention and intervention of BPD and provides a scientific basis for the government to formulate policies.