γ-羟丁酸钠对缺氧缺血后新生大鼠海马N-甲基-D-天冬氨酸受体2B亚基mRNA表达的影响

Effect of sodium gamma-hydroxybutyrate on expression of hippocampal N-methyl-D-aspartate receptor 2B subunit mRNA of hypoxic-ischemic neonatal rat

目的 探讨γ羟丁酸钠(GHB Na)对缺氧缺血后脑损伤新生大鼠有无保护作用及N 甲基 D 天冬氨酸受体2B亚基(NR2B)与脑损伤的关系。方法180只7日龄SD乳大鼠,随机分为5组(每组36只) ,分别为假手术(Sham)对照组、生理盐水(NS)对照组、GHB Na 5 0 ,10 0和2 0 0mg·kg- 1组。按Rice法制备缺氧缺血模型。Sham组仅分离颈总动脉,不结扎,不缺氧。GHB Na组动物于缺氧缺血后立即腹腔注射GHB Na。Sham组和NS组动物注射相同体积的生理盐水。以后每8h一次。在术后2 ,6 ,12 ,2 4h ,3和7d每组处死6只乳大鼠。应用逆转录 聚合酶链反应技术测定左侧海马组织中NR2BmRNA的表达,并进行半定量分析。结果 与Sham组相比,NS组术后2h ,NR2BmRNA的表达明显减少(约2 0 % ) ;在术后6 ,12 ,2 4h和3d ,NR2BmRNA的表达没有明显变化;术后7d ,NR2BmRNA的表达显著升高(约94 % )。与NS组相比,GHB Na 10 0mg·kg- 1组在术后6 ,12 ,2 4h ,3和7d ,NR2BmRNA的表达明显减少(分别减少约2 7% ,4 5 % ,19% ,31%和37% ) ;而GHB Na 5 0 ,2 0 0mg·kg- 1组的NR2BmRNA在这些时间点虽然也较NS组有不同程度的减少,但差异多无显著意义。结论 GHB Na能有效抑制新生大鼠缺氧缺血后海马NR2BmRNA的表达,特别是10 0mg·kg- 1组的抑制作用好于5 0和2 0 0mg·kg-

AIM To investigate if sodium gamma-hydroxybutyrate (GHB-Na) could protect neonatal rats from hypoxia-ischemia and the relationship between N-methyl-D-aspartate receptor 2B subunit (NR2B) expression and brain injury. METHODS One hundred and eighty Sprague Dawley rat pups of either sex weighing 10-14 g eighty seven-day old were randomly assigned to 5 groups (36 pups in every group): sham operation (Sham) group, normal saline (NS) group, GHB-Na 50 mg·kg -1 , GHB-Na 100 mg·kg -1 and GHB-Na 200 mg·kg -1 groups. The procedure for the induction of hypoxia-ischemia was carried out as described by Rice, et al. The pups of Sham were only underwent left carotid artery separation. The pups of GHB-Na and NS were administered ip GHB-Na and saline respectively, immediately after hypoxia and then repeated every 8 h. Reverse transcriptase polymerase chain reaction was used to analyze the expression of NR2B mRNA semi-quantificationally in the left hippocampus at 2, 6, 12, 24 h, and on 3 and 7 d after insulting. RESULTS Compared to Sham, expression of NR2B mRNA in NS was decreased by 20% at 2 h and increased significantly (about 94%) at 7 d. Compared to NS, the expression of NR2B mRNA in GHB-Na 100 mg·kg -1 group was decreased by 27%, 45%, 19%, 31% and 37% at 6, 12, 24 h, and on 3 and 7 d after insulting, respectively. GHB-Na 50 and 200 mg·kg -1 had no effects on the expression. CONCLUSION Systemically administration of GHB-Na 100 mg·kg -1 after hypoxia-ischemia can effectively suppress change of NR2B in neonatal rat hippocampus.