Cai Z, Hutchins J B, Rhodes P G
Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216-4505, USA.
Brain Res Dev Brain Res. 1998 Aug 8;109(2):265-9. doi: 10.1016/s0165-3806(98)00080-7.
The effects of intrauterine hypoxia-ischemia (HI) on nitric oxide synthase (NOS) activity and on expression of NOS isoforms were investigated in fetal and neonatal rat brains. Rat fetuses were subjected to either a 30-min intrauterine HI insult or a sham operation (SH) on gestational day 17 (G17). NOS activity in the homogenate of the rat brain was detectable on G17 and increased with age. NOS activity in the HI group was 20-30% higher than in the SH group from 6 to 48 h after the HI, but was 30% lower than in the SH group from postnatal day 8 to 14. Expression of the inducible NOS (iNOS) mRNA, as examined by RT-PCR, was increased as compared to the SH group from 6 to 24 h after the HI surgery. Expression of the constitutive neuronal NOS (nNOS) mRNA was reduced in the HI group from 24 h after the HI surgery up to postnatal day 14. Immunoblotting data have shown that alterations in NOS isoform protein expression caused by the intrauterine HI were consistent with the mRNA expression data. The overall results indicate that prenatal HI has long-lasting effects on function and expression of NOS in fetal and neonatal rat brains and that the altered NOS activity may be associated with prenatal HI-induced neurological abnormalities.
研究了宫内缺氧缺血(HI)对胎鼠和新生大鼠脑内一氧化氮合酶(NOS)活性及NOS亚型表达的影响。在妊娠第17天(G17),将胎鼠分为两组,一组进行30分钟的宫内HI损伤,另一组进行假手术(SH)。在G17时可检测到大鼠脑匀浆中的NOS活性,且其活性随年龄增长而增加。HI组在HI后6至48小时的NOS活性比SH组高20 - 30%,但在出生后第8天至14天比SH组低30%。通过逆转录聚合酶链反应(RT-PCR)检测发现,HI手术后6至24小时,诱导型NOS(iNOS)mRNA的表达与SH组相比有所增加。HI组在HI手术后24小时直至出生后第14天,组成型神经元NOS(nNOS)mRNA的表达均降低。免疫印迹数据表明,宫内HI引起的NOS亚型蛋白表达变化与mRNA表达数据一致。总体结果表明,产前HI对胎鼠和新生大鼠脑内NOS的功能和表达具有长期影响,且NOS活性的改变可能与产前HI诱导的神经异常有关。