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
LU Yan, LIU Xiao-Mei, LI Shu-Qin
Central Laboratory, Second Affiliated Hospital of China Medical University, Shenyang 110004, China. lisq1@cmu2h.com
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)×104 cps/μg RNA vs (21.28±3.54) ×104 cps/μg 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) ×104 cps/μg RNA (Model group) to (19.24±2.48)×104 cps/μg RNA (low dose group) or (17.35±2.30)×104 cps/μg 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.
LU Yan,LIU Xiao-Mei,LI Shu-Qin. 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[J]. CJCP, 2006, 8(4): 319-322.
