Ikeda Naho, Shoji Hiromichi, Suganuma Hiroki, Ohkawa Natsuki, Kantake Masato, Murano Yayoi, Sakuraya Koji, Shimizu Toshiaki
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan.
Pediatr Int. 2016 May;58(5):353-8. doi: 10.1111/ped.12855. Epub 2016 Feb 3.
Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period.
Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed.
Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA.
No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period.
胰岛素样生长因子-I（IGF-I）对围产期生长发育至关重要；宫内生长受限（IUGR）期间观察到血清IGF-I水平较低。我们研究了重组人（rh）IGF-I对出生后早期IUGR大鼠的影响。
通过结扎孕鼠双侧子宫动脉诱导宫内生长受限。将IUGR幼崽分为两组，从出生后第7天至13天每天注射rhIGF-I（2mg/kg；IUGR/IGF-I，n = 16）或生理盐水（IUGR/生理盐水溶液（PSS），n = 16）。将注射生理盐水的假手术孕鼠幼崽作为对照（对照，n = 16）。在出生后第25天测量血清IGF-I和IGF结合蛋白（IGFBP）3和5。在出生后第25天使用实时聚合酶链反应测量肝脏和大脑中Igf-i、IGF-I受体（Igf-ir）、Igfbp3和5 mRNA的表达。对肝脏进行IGF表达的免疫组织化学染色。
IUGR幼崽（IUGR/IGF-I和IUGR/PSS）出生后第3天和第25天的平均体重显著低于对照幼崽。IUGR幼崽的血清IGF-I和肝脏Igf-ir mRNA显著低于对照幼崽。在IUGR/IGF-I组中，肝脏Igfbp3 mRNA和肝脏免疫组织化学染色增加。在IUGR/PSS和对照幼崽中，这两组在血清IGFBP3和IGFBP5、肝脏Igf-i和Igfbp-5 mRNA或大脑Igf mRNA方面没有显著差异。
出生后早期用2mg/kg rhIGF-I治疗后，未观察到对体重和脑重增加有有益作用，但肝脏IGFBP-3有效增加。
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