PDF(Pubmed)
Abstract：
Intrauterine growth-restricted (IUGR) fetuses exhibit systemic inflammation that contributes to programmed deficits in myoblast function and muscle growth. Thus, we sought to determine if targeting fetal inflammation improves muscle growth outcomes. Heat stress-induced IUGR fetal lambs were infused with eicosapentaenoic acid (IUGR+EPA; n = 9) or saline (IUGR; n = 8) for 5 days during late gestation and compared to saline-infused controls (n = 11). Circulating eicosapentaenoic acid was 42% less (p < 0.05) for IUGR fetuses but was recovered in IUGR+EPA fetuses. The infusion did not improve placental function or fetal O2 but resolved the 67% greater (p < 0.05) circulating TNFα observed in IUGR fetuses. This improved myoblast function and muscle growth, as the 23% reduction (p < 0.05) in the ex vivo differentiation of IUGR myoblasts was resolved in IUGR+EPA myoblasts. Semitendinosus, longissimus dorsi, and flexor digitorum superficialis muscles were 24-39% lighter (p < 0.05) for IUGR but not for IUGR+EPA fetuses. Elevated (p < 0.05) IL6R and reduced (p < 0.05) β2 adrenoceptor content in IUGR muscle indicated enhanced inflammatory sensitivity and diminished β2 adrenergic sensitivity. Although IL6R remained elevated, β2 adrenoceptor deficits were resolved in IUGR+EPA muscle, demonstrating a unique underlying mechanism for muscle dysregulation. These findings show that fetal inflammation contributes to IUGR muscle growth deficits and thus may be an effective target for intervention.
摘要：
宫内生长受限（IUGR）胎儿表现出全身性炎症，导致成肌细胞功能和肌肉生长的程序性缺陷。因此，我们试图确定靶向胎儿炎症是否能改善肌肉生长结局.在妊娠后期，对热应激诱导的IUGR胎羊注入二十碳五烯酸（IUGREPA；n=9）或盐水（IUGR；n=8）5天，并与注入盐水的对照组（n=11）进行比较。IUGR胎儿的循环二十碳五烯酸减少了42％（p<0.05），但在IUGREPA胎儿中回收。输注不能改善胎盘功能或胎儿O2，但解决了在IUGR胎儿中观察到的67％以上（p<0.05）循环TNFα。这改善了成肌细胞功能和肌肉生长，IUGR成肌细胞离体分化的23%(p<0.05)在IUGR+EPA成肌细胞中得到解决。Semitendinosus,背长肌,对于IUGR，但对于IUGREPA胎儿，趾浅屈肌轻24-39％（p<0.05）。IUGR肌肉中IL6R升高（p<0.05）和β2肾上腺素受体含量降低（p<0.05）表明炎症敏感性增强，β2肾上腺素能敏感性降低。尽管IL6R仍然升高，β2肾上腺素受体缺陷在IUGR+EPA肌肉中得到解决，展示了肌肉失调的独特潜在机制。这些发现表明，胎儿炎症有助于IUGR肌肉生长缺陷，因此可能是干预的有效目标。
