This study aimed to explore whether dietary rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation to feed-restricted pregnant ewes counteracts fetal hepatic inflammation and innate immune dysfunction associated with intrauterine growth retardation (IUGR) in ovine fetuses. On d 35 of pregnancy, twin-bearing Hu ewes (n = 32) were randomly assigned to 4 treatment groups (8 ewes and 16 fetuses per group) and fed diets containing 100% of the NRC requirements (CON), 50% of the NRC requirements (RES), RES + RP-Arg (20 g/d) (RESA), or RES + NCG (5 g/d) (RESN). At 08:00 on d 110 of gestation, fetal blood and liver tissue samples were collected. The levels of triglyceride, free fatty acid, cholesterol and β-hydroxybutyrate in the fetal blood of RESA and RESN groups were lower (P < 0.05) than those of the RES group, but were higher (P < 0.05) than those of the CON group. The interleukin (IL)-6 and IL-1 levels in fetal blood and liver tissue as well as the myeloid differentiation primary response 88 (MyD88), transforming growth factor β (TGFβ), and nuclear factor kappa B (NF-κB) mRNA levels in the fetal liver were decreased (P < 0.05) by the NCG or RP-Arg supplementation compared to the RES treatment. Similarly, the toll-like receptor (TLR)-4, MyD88, TGFβ, and p-c-Jun N-terminal kinase (JNK) protein levels in the fetal liver were reduced (P < 0.05) in the NCG and RP-Arg -supplemented groups compared to the RES group. These results showed that dietary supplementation of RP-Arg or NCG to underfed pregnant ewes could protect against IUGR fetal hepatic inflammation via improving lipid metabolism, down-regulating the TLR-4 and the inflammatory JNK and NF-κB signaling pathways, and decreasing cytokine production in ovine fetal blood and liver tissue.

本研究旨在探讨在饲料限制的妊娠母羊中添加瘤胃保护的L-精氨酸 (RP-Arg) 或N-氨基甲酰谷氨酸 (NCG) 是否可以抵消与绵羊宫内发育迟缓 (IUGR) 相关的胎儿肝脏炎症和先天免疫功能障碍胎儿。在怀孕第 35 天，双胎胡母羊 ( n = 32) 被随机分配到 4 个治疗组（每组 8 只母羊和 16 只胎儿）并饲喂含有 100% NRC 需要量 (CON)、50% NRC 需要量 (RES)、RES + RP-Arg (20 g /d) (RESA)，或 RES + NCG (5 g/d) (RESN)。在妊娠第 110 天 08:00，采集胎儿血液和肝组织样本。RESA组和RESN组胎儿血中甘油三酯、游离脂肪酸、胆固醇和β-羟基丁酸的含量低于 RES组（P < 0.05），但高于RES组（P < 0.05) 高于 CON 组。胎儿血液和肝组织中的白细胞介素 (IL)-6 和 IL-1 水平以及骨髓分化初级反应 88 (MyD88)、转化生长因子 β (TGFβ) 和核因子κB (NF-κB) mRNA 与 RES 治疗相比，补充 NCG 或 RP-Arg降低了胎儿肝脏中的水平 ( P < 0.05)。同样，胎肝中toll样受体（TLR）-4、MyD88、TGFβ和pc-Jun N-末端激酶（JNK）蛋白水平降低（P < 0.05) 在 NCG 和 RP-Arg 补充组中与 RES 组相比。这些结果表明，在饮食不足的妊娠母羊中添加 RP-Arg 或 NCG 可以通过改善脂质代谢、下调 TLR-4 和炎症性 JNK 和 NF-κB 信号通路以及减少细胞因子的产生来预防 IUGR 胎肝炎症。在羊胎血和肝组织中。