地塞米松对内毒素休克新生大鼠脑一氧化氮合成酶基因表达的调节  

EFFECT OF DEXAMETHASONE ON REGULATION OF NITRIC OXIDE SYNHASES GENE EXPRESSIONS AFTER ENDOTOXIC SHOCK IN NEONATE RAT BRAIN

作　　者：王华[1] 吴玉斌[1] 杜秀华 

机构地区：[1]中国医科大学第二临床学院儿科,沈阳110004 [2]本溪市妇女儿童医院儿科,本溪117000

出　　处：《中国现代医学杂志》2003年第18期39-42,共4页China Journal of Modern Medicine

摘　　要：目的 :探讨新生大鼠内毒素休克脑损伤时脑 -氧化氮合成酶 (NOS)三种亚型基因表达的变化及地塞米松(DEX)对其的调控作用。方法 :在新生大鼠内毒素休克动物模型基础上 ,采用逆转录PCR及PCR技术 ,对脑组织中三型NOSmRNA及caspase - 3mRNA的表达进行半定量分析。结果 :正常新生大鼠脑iNOS及eNOSmRNA无明显表达 ,nNOSmRNA、caspase- 3mRNA有一定程度表达。内毒素脂多糖 (LPS)腹腔注射后 2h ,三种亚型NOSmRNA开始表达 ,于LPS 6h达高峰 ,并持续至 2 4h。caspase - 3mRNA于LPS腹腔注射后 2h后表达逐渐增加 ,2 4h达高峰。DEX可抑制nNOS、iNOS及caspase - 3mRNA的表达 ,且以用药后 2h最为明显 ,并持续至用药后 2 4h。结论 :内毒素休克脑损伤时 ,各型NOS均有表达 ,NO的产生是内毒素休克脑损伤时重要的病理生理机制之一。DEX通过抑制NOS、caspase - 3mRNA的表达部分实现其神经保护作用。Objective:To investigate the gene expression of three isoforms of nitric oxide synthases (NOSs) and effects of dexamethasone (DEX) on regulation of NOS gene expressions after endotoxic shock in neonate rat brain.Methods:Reverse transcriptase-PCR and PCR were used to analyze semi-quantitatively the expression of three isoforms of NOSs in the brain in neonatal rat endotoxic shock animal model.Results:Neuronal NOS (nNOS) and caspase-3 mRNA were expressed to some extent in normal neonate rat brain on post-natal day 7, whereas inducible and endothelial NOS (iNOS, eNOS) mRNA were rarely seen. The expression of threeisoforms of NOS mRNA was increased, peaked at 6h, and persistent to 24h after intraperitoneal administration of lipopolysaccharide (LPS) by 5mg/mg. Expression of nNOS, iNOS, and caspase-3 mRNA was inhibited by DEX administered with LPS concomitantly, which marked at 2h after DEX delivery and lasted to 24h. Conclusion:Three isoforms of NOS mRNA co-expressed in the brain during endotoxic shock and NO production may be one of the important pathophysiological mechanisms leading to brain injury during endotoxic shock. Neuroprotective role of DEX may be realized partially through inhibiting the expression of three isoforms of NOS and caspase-3 which is a potent effector inducing cell apoptosis.

关 键 词：内毒素 休克 脑 一氧化氮合成酶 caspase—3 地塞米松 新生 大鼠 

分 类 号：R969.4[医药卫生—药理学]