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[L-精氨酸对宫内生长迟缓大鼠胰岛素样生长因子及胰岛素样生长因子结合蛋白3表达的影响]

[Effects of L-arginine on the expression of insulin-like growth factors and insulin-like growth factor binding protein 3 in rats with intrauterine growth retardation].

作者信息

Lu Yan, Liu Xiao-Mei, Li Shu-Qin

机构信息

Central Laboratory, Second Affiliated Hospital of China Medical University, Shenyang 110004, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2006 Aug;8(4):319-22.

Abstract

OBJECTIVE

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.

METHODS

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).

RESULTS

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).

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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)。

结论

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。

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