Biotron Research Centre, London, Ontario, Canada.
Department of Pathology and Laboratory Medicine, The University of Western Ontario, London, Ontario, Canada.
J Dev Orig Health Dis. 2021 Dec;12(6):915-922. doi: 10.1017/S2040174420001269. Epub 2020 Dec 23.
Although abundant evidence exists that adverse events during pregnancy lead to chronic conditions, there is limited information on the impact of acute insults such as sepsis. This study tested the hypothesis that impaired fetal development leads to altered organ responses to a septic insult in both male and female adult offspring. Fetal growth restricted (FGR) rats were generated using a maternal protein-restricted diet. Male and female FGR and control diet rats were housed until 150-160 d of age when they were exposed either a saline (control) or a fecal slurry intraperitoneal (Sepsis) injection. After 6 h, livers and lungs were analyzed for inflammation and, additionally, the amounts and function of pulmonary surfactant were measured. The results showed increases in the steady-state mRNA levels of inflammatory cytokines in the liver in response to the septic insult in both males and females; these responses were not different between FGR and control diet groups. In the lungs, cytokines were not detectable in any of the experimental groups. A significant decrease in the relative amount of surfactant was observed in male FGR offspring, but this was not observed in control males or in female animals. Overall, it is concluded that FGR induced by maternal protein restriction does not impact liver and lung inflammatory response to sepsis in either male or female adult rats. An altered septic response in male FGR offspring with respect to surfactant may imply a contribution to lung dysfunction.
虽然有大量证据表明妊娠期间的不良事件会导致慢性疾病，但关于急性损伤（如败血症）对其的影响的信息有限。本研究检验了这样一个假设，即胎儿发育不良会导致雄性和雌性成年后代的器官对败血症的急性损伤产生不同的反应。使用母体蛋白限制饮食来生成胎儿生长受限（FGR）大鼠。雄性和雌性 FGR 以及对照饮食大鼠被饲养至 150-160 日龄，然后接受生理盐水（对照）或粪便浆剂腹腔内（败血症）注射。6 小时后，分析肝脏和肺部的炎症，并测量肺表面活性剂的量和功能。结果显示，雄性和雌性大鼠的肝脏对败血症的急性损伤均有炎症细胞因子的稳态 mRNA 水平增加；FGR 和对照饮食组之间没有差异。在肺部，实验组均未检测到细胞因子。雄性 FGR 后代的表面活性剂相对量显著减少，但在对照雄性或雌性动物中未观察到。总体而言，结论是母体蛋白限制引起的 FGR 不会影响雄性或雌性成年大鼠的肝脏和肺对败血症的炎症反应。雄性 FGR 后代对表面活性剂的败血症反应改变可能意味着对肺功能障碍有一定的影响。
