周容
四川大學華西第二醫院教授、主任醫師、博士生導師
發表核心期刊論文200餘篇,SCI論文60餘篇。
Low Expression of FGF23 and Its Effect on Rats with Intrauterine Growth Retardation
Author: Gui, Shun-Ping; Zou, Heng; Bai, Yi; Liu, Min; Wang, Tao; Zhou, Rong.
Citation: Gui, Shun-Ping; Zou, Heng; Bai, Yi; Liu, Min; Wang, Tao; Zhou, Rong. Low Expression of FGF23 and Its Effect on Rats with Intrauterine Growth Retardation. Maternal-Fetal Medicine. 2020; 2(4): P211-216. doi: 10.1097/FM9.0000000000000066
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Abstract
Objective: To explore the levels of fibroblast growth factor 23 (FGF23) during pregnancy and its relationship with intrauterine growth restriction (IUGR).Methods: Pregnant rats were classified into an ad libitum rat chow group (ad libitum rat chow, AD group, n = 25) and an undernutrition group (50% of their daily food requirement, UN group, n = 25). The levels of maternal serum FGF23, tissue homogenate FGF23, and bone gla protein in fetal rats, and placental FGF23 mRNA and protein expression were examined by enzyme-linked immunosorbent assay, real-time qPCR analysis respectively. Finally, the effect of recombinant FGF23 on the viability of MG-63 cells was determined by cell proliferation assay. Data were analyzed with independent two-tailed t test and one-way analysis of variance. Spearman rank- order correlation coefficients (continuous variables) was performed to determine the relationship of results.Results: The diet restriction induced IUGR in rat offsprings, and the UN group exhibited a significantly lower FGF23 level (P < 0.05, n = 25). The FGF23 level was increased and peaked in maternal serum on gestation day (GD) 15, but peaked in fetal and placenta on GD20. Moreover, the tissue homogenate levels of FGF23 and bone gla protein in fetal rats in both groups were positively correlated (r = 0.923, P < 0.05; r = 0.925, P < 0.05, respectively, n = 25), FGF23 was localized to both decidual and labyrinth zones, with remarkably higher expression on GD20, P < 0.05, n = 25. In vitro, recombinant human FGF23 enhanced MG-63 cell viability, P < 0.05, n = 25.Conclusion: Prenatal undernutrition could decrease the FGF23 expression in fetal rats caused by the mother through the placenta, and induced the IUGR and hindered the ossification. And the FGF23 levels are peaked on GD15 mother but peaked on GD20 placenta and fetuses, these might be associated with the over compensation of maternal placenta on GD20.Highlights
Provided evidence that prenatal undernutrition could decrease the FGF23 expression in fetal rats caused by the mother through the placenta, and induced the IUGR and hindered the ossification.
Found that the FGF23 levels are peaked on GD15 mother but peaked on GD20 placenta and fetuses.
Suggesting that the FGF23 level are peaked in different gestation days might be associated with the over compensation of maternal placenta.
摘要
目的:探討妊娠期間成纖維細胞生長因子23(fibroblast growth factor 23, FGF23)表達水平的變化及其與宮內生長受限(intrauterine growth restriction, IUGR)的關係。
方法:將妊娠大鼠分為自由飲食組(ad libitum rat chow group, AD組)和營養不良組(給予其每日食物需求量的50%;undernutrition group, UN組)。通過酶聯免疫吸附試驗, 實時螢光定量PCR,檢測在不同時間點的母鼠血清中FGF23水平,胎鼠骨組織勻漿內FGF23和骨鈣素水平,以及胎盤FGF23 mRNA和蛋白的表達。最後,通過測定經重組蛋白FGF23處理後成骨樣MG-63細胞增殖能力的變化,來評價重組蛋白FGF23對其產生的影響。數據採用t檢驗和單因素方差分析,和Spearman相關性分析分別進行統計學分析
結果:孕期飲食限制導致胎鼠體重減輕和身長縮短,即子代IUGR,且FGF23水平顯著降低(P <0.05)。免疫結果顯示,FGF23位於胎盤的蛻膜區和迷路區。FGF23水平在妊娠第15天(gestation day, GD)時,在母體血清中升高並達到峰值;而在GD20時,在胎兒和胎盤中達到峰值。此外,兩組胎鼠中FGF23和骨鈣素的組織勻漿水平呈正相關(r = 0.923, P <0.05; r = 0.925, P <0.05)。在體外細胞實驗證實,重組人FGF23蛋白可增強MG-63細胞的增殖能力, P < 0.05, n = 25。
結論:孕期營養不足可致母體FGF23水平降低,並通過胎盤降低胎兒的FGF23表達水平,引起IUGR及骨化障礙。本文中,FGF23水平在母體上於GD15達到峰值,但在胎盤和胎兒上於GD20達到峰值,這可能與GD20母體胎盤的過度代償有關。