Lu Yan, Liu Xiao-Mei, Li Shu-Qin
Central Laboratory, Second Affiliated Hospital of China Medical University, Shenyang 110004, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2006 Aug;8(4):319-22.
Intrauterine growth retardation (IUGR) may contribute to the disorder of development of fetal brains. L-arginine has been known to be effective in blood vessel distension and improving the blood circulation of placentas. Recent studies have shown that L-arginine can ameliorate the placental hypoxia and improve the development of fetus. This study aimed to explore the effects of L-arginine on the expression of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein-3(IGFBP3)and IGF-I mRNA in brains of IUGR rats and the possible mechanisms of L-arginine.
Thirty-six pregnant rats were randomly assigned into four groups: Control, Model, Low dose L-arginine (100 mg/kg) and High-dose L-arginine (200 mg/kg L-arginine) groups (n=9 each). IUGR was induced by passive smoking in rats from the last three groups. L-arginine was administered for the last two groups between days 8 and 20 of gestation. On day 21 of gestation, the pup rats were delivered by cesarean section. The levels of IGF-I, IGF-II and IGFBP3 in the brains of pup rats were measured by enzyme-linked immunoadsordent assay (ELISA) and the expression of IGF-I mRNA was detected by fluorescence quantitative PCR (FQ-PCR).
The levels of IGF-I, IGF-II and IGF-I mRNA expression in the Model group were significantly lower than in the Control group, with the IGF-I levels of 0.789 +/- 0.062 ng/mg vs 0.947 +/- 0.042 ng/mg, the IGF-II levels of 0.270 +/- 0.020 ng/mg vs 0.374 +/- 0.015 ng/mg and the IGF-I mRNA expression of (13.12 +/- 1.39) x 10(4) cps/mug RNA vs (21.28 +/- 3.54) x 10(4) cps/mug RNA (P < 0.01). In contrast, the IGFBP3 levels in the Model group were significantly higher than in the Control group (0.253 +/- 0.011 ng/mg vs 0.089 +/- 0.015 ng/mg; P < 0.01). Low or high dose L-arginine treatment increased significantly the IGF-I levels from 0.789 +/- 0.062 ng/mg (Model group) to 0.937 +/- 0.067 ng/mg (low dose group) or 0.858 +/- 0.077 ng/mg (high dose group), the IGF-II levels from 0.270 +/- 0.020 ng/mg (Model group) to 0.318 +/- 0.018 ng/mg (low dose group) or 0.354 +/- 0.021 ng/mg (high dose group) and the IGF-I mRNA expression from (13.12 +/- 1.39) x 10(4) cps/mug RNA (Model group) to (19.24 +/- 2.48) x 10(4) cps/mug RNA (low dose group) or (17.35 +/- 2.30) x 10(4) cps/mug RNA (high dose group) (P < 0.01). The IGFBP3 levels were significantly reduced after low or high dose L-arginine treatment (0.132 +/- 0.006 ng/mg or 0.146 +/- 0.009 ng/mg) compared with those of the Model group (0.253 +/- 0.011 ng/mg) ( P < 0.01).
L-arginine can increase the levels of IGF-I and IGF-II and the IGF-I mRNA expression, and decrease the IGFBP3 level in the brain of rats with IUGR induced by passive smoking, thereby offering protective effects against IUGR.
宫内生长受限（IUGR）可能导致胎儿脑发育紊乱。已知L-精氨酸在血管扩张及改善胎盘血液循环方面有效。近期研究表明，L-精氨酸可改善胎盘缺氧并促进胎儿发育。本研究旨在探讨L-精氨酸对IUGR大鼠脑内胰岛素样生长因子（IGF）-I、IGF-II、IGF结合蛋白-3（IGFBP3）及IGF-I mRNA表达的影响及其可能机制。
36只孕鼠随机分为四组：对照组、模型组、低剂量L-精氨酸（100 mg/kg）组和高剂量L-精氨酸（200 mg/kg）组（每组n = 9）。后三组大鼠通过被动吸烟诱导IUGR。在妊娠第8至20天对后两组给予L-精氨酸。妊娠第21天，通过剖宫产娩出幼鼠。采用酶联免疫吸附测定（ELISA）法检测幼鼠脑内IGF-I、IGF-II和IGFBP3水平，采用荧光定量PCR（FQ-PCR）法检测IGF-I mRNA表达。
模型组IGF-I、IGF-II水平及IGF-I mRNA表达均显著低于对照组，IGF-I水平分别为0.789±0.062 ng/mg和0.947±0.042 ng/mg，IGF-II水平分别为0.270±0.020 ng/mg和0.374±0.015 ng/mg，IGF-I mRNA表达分别为（13.12±1.39）×10⁴ cps/μg RNA和（21.28±3.54）×10⁴ cps/μg RNA（P < 0.01）。相反，模型组IGFBP3水平显著高于对照组（0.253±0.011 ng/mg对0.089±0.015 ng/mg；P < 0.01）。低剂量或高剂量L-精氨酸处理后，IGF-I水平从模型组的0.789±0.062 ng/mg显著升高至低剂量组的0.937±0.067 ng/mg或高剂量组的0.858±0.077 ng/mg，IGF-II水平从模型组的0.270±0.020 ng/mg升高至低剂量组的0.318±0.018 ng/mg或高剂量组的0.354±0.021 ng/mg，IGF-I mRNA表达从模型组的（13.12±1.39）×10⁴ cps/μg RNA升高至低剂量组的（19.24±2.48）×10⁴ cps/μg RNA或高剂量组的（17.35±2.30）×10⁴ cps/μg RNA（P < 0.01）。与模型组（0.253±0.011 ng/mg）相比，低剂量或高剂量L-精氨酸处理后IGFBP3水平显著降低（0.132±0.006 ng/mg或0.146±0.009 ng/mg）（P < 0.01）。
L-精氨酸可提高被动吸烟诱导的IUGR大鼠脑内IGF-I和IGF-II水平及IGF-I mRNA表达，降低IGFBP3水平，从而对IUGR起到保护作用。
