Xu Yan, Liu Ming-Chao, Wang Pei, Xu Bei, Liu Xin-Qin, Zhang Zhi-Ping, Ren Li-Fen, Qin Qing, Ma Yue-Yun, Luo Wen-Jing, Hao Xiao-Ke
Department of Clinical Laboratories, Xijing Hospital, Fourth Military Medical University Xi'an 710032, China.
Department of Occupational & Environmental Health and The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University Xi'an 710032, China.
Int J Clin Exp Med. 2014 Apr 15;7(4):856-64. eCollection 2014.
This study aimed to investigate correlation between serum insulin-like growth factor-1 (IGF-1) and blood lead level in short stature children with growth hormone deficiency (GHD), and IGF-1 signal molecules were investigated in lead exposed rats. Our findings may provide evidence for clarifying pathogenesis of lead induced short stature in children.
880 short stature children were recruited from clinics and divided into GHD group and idiopathic short stature (ISS) group according to the GH peak in growth hormone stimulation test. The height, body weight, serum IGF-1 level and blood lead level were determined. A rat model of lead poisoning was used to establish and western blot assay was employed to detect the phosphorylation of signaling molecules (MAPK and PI3K/Akt) related to IGF-1 signaling pathway.
In GHD group, the height, body weight and serum IGF-1 level were significantly lower, but the blood lead level was significantly higher than those in ISS group (P<0.05). Western blot assay confirmed that the protein expression of phosphorylated ERK1/2, JNK, p38, Akt473 and Akt308 increased significantly (P<0.01) in lead exposure rats.
Our study suggesting that reduction in IGF-1 in children with GHD is associated with blood lead level. Lead exposure may induce expression of phosphorylated MAPK and Akt signaling molecules. The activation of these molecules may influence binding of IGF-1 and tyrosine kinase receptor IGFIR to regulate cell growth via the MAPK and Akt signaling pathways, which then interfere with growth-promoting effect of IGF-1 in short children.
本研究旨在探讨生长激素缺乏（GHD）所致身材矮小儿童血清胰岛素样生长因子-1（IGF-1）与血铅水平之间的相关性，并对铅暴露大鼠的IGF-1信号分子进行研究。我们的研究结果可能为阐明儿童铅中毒致身材矮小的发病机制提供依据。
从门诊招募880例身材矮小儿童，根据生长激素刺激试验中的生长激素峰值分为GHD组和特发性身材矮小（ISS）组。测定身高、体重、血清IGF-1水平和血铅水平。采用铅中毒大鼠模型，并用蛋白质印迹法检测与IGF-1信号通路相关的信号分子（MAPK和PI3K/Akt）的磷酸化水平。
GHD组的身高、体重和血清IGF-1水平显著低于ISS组，但血铅水平显著高于ISS组（P<0.05）。蛋白质印迹法证实，铅暴露大鼠中磷酸化ERK1/2、JNK、p38、Akt473和Akt308的蛋白表达显著增加（P<0.01）。
我们的研究表明，GHD儿童IGF-1水平降低与血铅水平有关。铅暴露可能诱导磷酸化MAPK和Akt信号分子的表达。这些分子的激活可能影响IGF-1与酪氨酸激酶受体IGFIR的结合，通过MAPK和Akt信号通路调节细胞生长，进而干扰IGF-1对矮小儿童的促生长作用。
