Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
Pediatr Res. 2021 Oct;90(4):768-775. doi: 10.1038/s41390-020-01334-0. Epub 2021 Jan 19.
Necrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature neonates. Possible therapeutic approaches are centered on promoting maturation of the gastrointestinal mucosal barrier. Studies have demonstrated that antenatal administration of corticosteroids can decrease NEC incidence and mortality.
Pregnant rat dams were administered dexamethasone 48 h prior to delivery. The pups were subjected to an experimental NEC-like injury protocol. Ileal tissues and sera were collected and evaluated for inflammatory cytokines, gut permeability and expressions and localizations of tight junction proteins, and surfactant protein-D by immunohistochemistry/immunofluorescent staining. Intestinal epithelial cells (IEC-6) were pretreated with SP-D to examine the effect of SP-D on tight junction protein expressions when challenged with platelet-activating factor and lipopolysaccharide to model proinflammatory insults.
Antenatal dexamethasone reduced systemic inflammation, preserved intestinal barrier integrity, and stimulated SP-D expression on the intestinal mucosal surface in pups exposed to NEC-like injury. Pretreatment of SP-D blocked platelet-activating factor/lipopolysaccharide-induced tight junction disruption in IEC-6 cells in vitro.
Antenatal dexamethasone preserves the development of intestinal mucosal barrier integrity and reduces incidence and morbidity from an experimental NEC-like injury model. Dexamethasone upregulation of intestinal SP-D-protective effects on tight junction proteins.
Antenatal administration of dexamethasone can function in concert with intestinal surfactant protein-D to decrease systemic inflammatory responses, and protect intestinal barrier integrity in a neonatal rat model of NEC. A novel role of intestinal SP-D in preserving tight junction protein structures under inflammatory conditions. We describe the intestinal SP-D-an overlooked role of antenatal dexamethasone in neonatal NEC?
坏死性小肠结肠炎（NEC）是早产儿最常见的胃肠道疾病。可能的治疗方法集中在促进胃肠道黏膜屏障的成熟上。研究表明，产前给予皮质类固醇可以降低 NEC 的发病率和死亡率。
妊娠大鼠在分娩前 48 小时给予地塞米松。将幼崽置于实验性 NEC 样损伤方案中。收集回肠组织和血清，通过免疫组化/免疫荧光染色评估炎症细胞因子、肠道通透性以及紧密连接蛋白和表面活性蛋白-D 的表达和定位。用表面活性蛋白-D 预处理肠上皮细胞（IEC-6），当用血小板激活因子和脂多糖模拟促炎损伤时，观察表面活性蛋白-D 对紧密连接蛋白表达的影响。
产前地塞米松降低了全身炎症反应，在暴露于 NEC 样损伤的幼崽中维持了肠道屏障的完整性，并刺激了肠道黏膜表面的表面活性蛋白-D 表达。表面活性蛋白-D 的预处理阻断了血小板激活因子/脂多糖诱导的 IEC-6 细胞中紧密连接的破坏。
产前地塞米松可维持肠道黏膜屏障完整性的发育，并降低实验性 NEC 样损伤模型的发生率和发病率。地塞米松上调肠道表面活性蛋白-D 对紧密连接蛋白的保护作用。
产前给予地塞米松可以与肠道表面活性蛋白-D 协同作用，减少全身炎症反应，并保护新生儿 NEC 模型中的肠道屏障完整性。肠道表面活性蛋白-D 在炎症条件下维持紧密连接蛋白结构的新作用。我们描述了肠道表面活性蛋白-D-产前地塞米松在新生儿 NEC 中被忽视的作用？
