Arginyl-Glutamine Dipeptide or Docosahexaenoic Acid Attenuates Hyperoxia-induced Small Intestinal Injury in Neonatal Mice

作者：Li Nan; Ma Liya; Liu Xueyan; Shaw Lynn; Calzi Sergio Li; Grant Maria B; Neu Josef^*

来源：Journal of Pediatric Gastroenterology and Nutrition, 2012, 54(4): 499-504.

DOI：10.1097/MPG.0b013e3182330867

• arginine
• dipeptide
• docosahexaenoic acid
• glutamine
• intestinal injury

Background and Objective: Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates; however, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model.
Methods: Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 days. After 5 days of hyperoxic exposure (P-7-P-12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 days (P-12-P-17). Mouse pups received Arg-Gln (5 g . kg(-1) . day(-1)) or DHA (5 g . kg(-1) . day(-1)) or vehicle orally started on P-12 through P-17. Distal small intestine (DSI) histologic changes, myeloperoxidase (MPO), lactate dehydrogenase (LDH), inflammatory cytokines, and tissue apoptosis were evaluated.
Results: Hyperoxic mice showed a greater distortion of overall villus structure and with higher injury score (P< 0.05). Arg-Gln dipeptide and DHA supplementation groups were more similar to the room air control group. Supplementation of Arg-Gln or DHA reduced hyperoxia-induced MPO activity (P < 0.05). Supplementation of Arg-Gln or DHA returned LDH activity to the levels of control. Hyperoxia induced apoptotic cell death in DSIs, and both Arg-Gln and DHA reversed this effect (P < 0.05).
Conclusions: Supplementation with either Arg-Gln or DHA may limit some inflammatory and apoptotic processes involved in hyperoxic-induced intestinal injury in neonatal mice.

• 出版日期2012-4