孕鼠铁缺乏对子代GH-IGF-1轴的影响

Effect of iron deficiency in pregnant rat on GH-IGF-1 axis of offspring

摘要:

目的  探讨大鼠妊娠期铁缺乏对新生仔鼠生长激素-胰岛素样生长因子-1（GH-IGF-1）轴的影响及机制。方法  4周龄雌性Wistar大鼠36只，随机分为实验组和对照组，分别饲低铁饲料和含铁饲料喂养4周，检测雌鼠血红蛋白（Hb）浓度，血细胞比容（HCT）、红细胞平均容积（MCV）、红细胞平均血红蛋白量（MCH）、红细胞平均血红蛋白浓度（MCHC）及红细胞分布宽度（RDW）等血液学相关参数。将雌鼠与正常雄鼠合笼，孕末期检测血液学相关参数并行骨髓铁染色。观察仔鼠存活率及体重。实时荧光定量聚合酶链式反应（qRT-PCR）方法检测新生仔鼠垂体生长激素（GH）及肝脏胰岛素样生长因子-1（IGF-1）表达量。结果  相比对照组，实验组低铁干预4周后孕鼠孕末期Hb、HCT、MCV、MCH及MCHC等水平降低（P <0.05），RDW水平升高（P <0.05）；实验组大鼠骨髓细胞内铁及外铁减少；实验组新生仔鼠体重及仔鼠存活率低于对照组（P <0.05）；实验组垂体GH信使核糖核酸（mRNA）及肝脏IGF-1 mRNA的表达低于对照组（P <0.05）。结论  妊娠期铁缺乏下调子代GH和IGF-1 mRNA表达造成子代低出生体重。

Abstract:

Objective To explore how iron deficiency in pregnant rats affected GH-IGF-1 axis of offspring and its mechanism. Methods Four-week-old healthy female Wistar rats were randomly divided into experimental group (n = 18) and control group (n = 18). The rats of the experimental group were fed with low iron diet, while the control group were fed with normal diet. After four weeks, according to the 2 : 1 ratio, the rats were mated with healthy adult male rats. Hematological parameters of the rats' eye vein blood were detected, including hemoglobin (Hb), haematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell distribution width (RDW). Pregnant rats were randomly drawn from each group to measure the iron of bone marrow. The survival rate and weight of newborn rat offspring were observed. The mRNA expressions of growth hormone (GH) in pituitary and insulin-like growth factor-1 (IGF-1) in liver of newborn rats were assessed by quantitative real-time PCR. Results The levels of Hb, HCT, MCV, MCH and MCHC in the experimental group were significantly lower (P < 0.05) than those of the control group, while RDW increased remarkably (P < 0.05). In the experimental group, iron in pregnant rats' bone marrow decreased significantly more than that in the control group, compared with which, the survival rate, weight, and the expression of GH mRNA and IGF-1 mRNA of offspring decreased significantly (P < 0.05) in the experimental group. Conclusions Iron deficiency during pregnancy leads to low birth weight through down-regulating the expression of GH mRNA and IGF-1 mRNA of offspring.