Zhong Jingren, Bæk Ole, Doughty Richard, Jørgensen Benjamin Meyer, Jensen Henrik Elvang, Thymann Thomas, Sangild Per Torp, Brunse Anders, Nguyen Duc Ninh
Comparative Pediatrics, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
Department of Pathology, Akershus University Hospital, Lørenskog, Norway.
Biochim Biophys Acta Mol Basis Dis. 2025 Apr;1871(4):167723. doi: 10.1016/j.bbadis.2025.167723. Epub 2025 Feb 18.
Premature infants are highly susceptible to infections that can lead to sepsis with life-threatening organ dysfunctions. The clinical practice of high parenteral glucose supply in preterm infants can exacerbate infection outcomes through excessive glycolysis-induced inflammatory response. This in turn can affect the health of vital preterm organs, including the brain and kidneys. We hypothesized that reduced parenteral glucose supply to infected preterm newborns may help protect against pathology in these two key organs.
Cesarean-delivered preterm pigs were nourished with high or low parenteral glucose levels (21 % vs. 5 %), infused with Staphylococcus epidermidis or saline, and monitored in heated, oxygenated incubators until 22 h. Blood, brain, and kidney samples were collected for histological, immunohistological, q-PCR, ELISA, and biochemical analyses.
Infection led to multiple pathological changes (e.g. edema), increased inflammation and tissue injury (indicated by gene expression data) in both brain and kidneys of preterm piglets. Reduced glucose supply in infected animals alleviated histopathological manifestations in the brain, and reduced neuroinflammation with enhanced M2 microglial phenotype. Reduced glucose supply also decreased plasma creatinine, and the severity of renal edema, tubular vacuolization and dilatation. Multiple genes related to innate and Th1 immunity in both organs were dampened by reduced glucose supply. Correlation analysis showed that renal inflammation was more closely connected to systemic inflammation compared to neuroinflammation.
Reduced glucose supply can reduce renal and neuro-inflammation during neonatal infection, thereby protecting brain and kidney health in infected preterm neonates.
早产儿极易感染，感染可导致败血症并伴有危及生命的器官功能障碍。早产儿高肠外葡萄糖供应的临床实践可通过过度糖酵解诱导的炎症反应加剧感染后果。这进而会影响包括脑和肾在内的重要早产儿器官的健康。我们推测，减少感染的早产新生儿的肠外葡萄糖供应可能有助于预防这两个关键器官的病变。
剖宫产出生的早产仔猪分别用高或低肠外葡萄糖水平（21%对5%）喂养，注入表皮葡萄球菌或生理盐水，并在加热、充氧的培养箱中监测至22小时。采集血液、脑和肾样本进行组织学、免疫组织学、q-PCR、ELISA和生化分析。
感染导致早产仔猪脑和肾出现多种病理变化（如水肿），炎症和组织损伤增加（由基因表达数据表明）。感染动物中葡萄糖供应减少减轻了脑的组织病理学表现，并通过增强M2小胶质细胞表型减少了神经炎症。葡萄糖供应减少还降低了血浆肌酐以及肾水肿、肾小管空泡化和扩张的严重程度。两个器官中与先天免疫和Th1免疫相关的多个基因因葡萄糖供应减少而受到抑制。相关性分析表明，与神经炎症相比，肾炎症与全身炎症的联系更为紧密。
减少葡萄糖供应可减轻新生儿感染期间的肾和神经炎症，从而保护感染的早产新生儿的脑和肾健康。
