产前补充牛磺酸对宫内生长受限胎鼠脑组织PKA-CREB通路及GDNF mRNA表达的影响

Effects of prenatal taurine on mRNA expression of PKA-CREB signal pathway and glial cell line-derived neurotrophic factor in fetal rat brains of intrauterine growth restriction

目的探讨牛磺酸对宫内生长受限(IUGR)胎鼠大脑蛋白激酶A-cAMP反应元件结合蛋白(PKA-CREB)通路及胶质细胞源性神经营养因子(GDNF)mRNA表达的影响。方法采用妊娠期全程饥饿法制作IUGR模型,将20只孕鼠随机分为4组(n=5):对照组、IUGR组、小剂量(每天100mg/kg)及大剂量(每天300mg/kg)牛磺酸用药组。利用逆转录-聚合酶链反应方法检测各组胎鼠大脑PKA、CREB及GDNF mRNA水平变化。结果与对照组相比,IUGR组胎鼠大脑PKA、CREB及GDNF mRNA表达均明显增多(P<0.05)。与IUGR组相比,小剂量和大剂量牛磺酸组胎鼠脑组织的PKA和CREB mRNA表达水平增高(P<0.05),大剂量牛磺酸组胎鼠脑组织GDNF mRNA水平亦明显增高(P<0.01)。结论牛磺酸可增加IUGR胎鼠大脑PKA-CREB通路及GDNF mRNA的表达,提示产前补充牛磺酸可能通过增强中枢神经系统神经发生能力、增加神经营养因子的分泌等途径来改善IUGR胎鼠脑损伤,发挥对脑组织的保护作用。

Objective This study examined the effects of prenatal application of taurine on mRNA expression of protein kinase A-cAMP response element binding protein （PKA-CREB） signal pathway and glial cell line-derived neurotrophic factor （GDNF） in fetal rat brains of intrauterine growth restriction （IUGR）. Methods Pregnant rats were randomly divided into 4 groups： normal control, IUGR model, low-dose （100 mg/kg · d） and high-dose （300 mg/kg · d） taurine treatment IUGR （n = 5 each）. IUGR was induced by food restriction throughout pregnancy. PKA, CREB and GDNF mRNA expression in brains of newborn rats was detected by reverse transcription-polymerase chain reaction （ RT- PCR）. Results PKA, CREB and GDNF mRNA expression in the IUGR model group was significantly higher than that in the normal control group （P 〈 0.05）. Compared with the IUGR model group, mRNA expression of PKA and CREB in both the low-dose and high-dose taurine treatment groups increased significantly （ P 〈 0.05 ） ; GDNF mRNA expression in the high-dose taurine treatment group also increased significantly （ P 〈 0.01 ）. Conclusions Taurine can increase mRNA expression of PKA, CREB and GDNF in fetal rat brains of IUGR. This suggests that prenatal application of taurine may increase neurogenesis of the central nervous system and endogenous secretion of neurotrophic factors, thus providing neuroprotective effects.