摘要目的：通过观察黄芪总苷和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂对宫内窘迫诱发的缺血缺氧强应激后新生鼠 Tau 蛋白超磷酸化的影响，探讨两者对 Tau 蛋白超磷酸化的调节，并比较其作用途径，以期为改善宫内窘迫诱发的认知障碍的机制提供研究思路。方法采用2×3析因设计：即宫内窘迫（2水平：无处置、施行宫内窘迫即夹闭孕鼠的子宫动脉2／3持续10 min）和药物（3水平：尾静脉注射0．9％氯化钠注射液、NMDA 受体拮抗剂 MK-801、黄芪总苷）的所有组合。宫内窘迫处置结束后母鼠继续妊娠至新生鼠剖宫产娩出，待新生鼠生长至12周时留取海马，HPLC 法检测谷氨酸在海马中的含量，IHC-SP 法检测 p-AT8Ser202和 GSK-3β1H8的表达。结果宫内窘迫可增加海马内谷氨酸的浓度（P ＜0．05）；黄芪总苷可降低宫内窘迫诱发的过度升高的谷氨酸浓度，且两者有相减效果（P ＜0．05）；而 NMDA 受体拮抗剂对海马中谷氨酸的浓度无明显影响（P ＜0．05）。宫内窘迫可增加海马内 p-AT8Ser202以及促进 Tau 蛋白超磷酸化的调控蛋白 GSK-3β1H8的表达（P ＜0．05）；黄芪总苷和 NMDA 受体拮抗剂可减缓海马内 p-AT8Ser202及促进其磷酸化的 GSK-3β1H8表达上调（P ＜0．05）；两者效果相似且和宫内窘迫诱发的缺血缺氧强应激的影响呈相减效果（P ＜0．05）。结论黄芪总苷可通过降低谷氨酸浓度减缓 Tau 蛋白磷酸化；GSK-3β是该信号通路的关键蛋白；黄芪总苷改善认知功能的效果优于 NMDA 受体拮抗剂。

abstractsObjective To explore the reversion of astragaloside and NMDA receptor antagonist against the hyperphosphorylation of protein Tau induced by fetal intrauterine distress in neonatal rats.Methods The analysis of variance of factorial design was setted up two intervention factors which were fetal intrauterine distress (two levels:no disposition;a course of fetal intrauterine distress)and the drugs (three levels:iv Saline;iv astragaloside;iv MK -801).When the neonatal rats grew to 12weeks,the hippocampus was removed from the neonatal rats.Detected the content of glutamate in the hippocampus of rats by high performance liquid chromatography.The expression of protein Tau which includes p -AT8Ser202 and GSK -3β1H8 in the hippocampus of rats were detected by the methods of immunohistochemistry staining.Results Fetal intrauterine distress could significantly up -regulate the content of glutamate,which was not affected by MK -801,in the hippocampus of neonatal rats which was reduces by the astragaloside (P <0.05).And both influences presented subtracting effects (P <0.05).Fetal intrauterine distress and the drugs do not affect the total protein Tau in the hippocampus of rats (P <0.05).Fetal intrauterine distress could up -regulate the hyperphosphorylation of protein Tau in the hippocampus of neonatal rats which could be reduced by astragaloside and MK -801 (P <0.05).And the influences between fetal intrauterine distress and the drugs presented subtracting effects (P <0.05 ).Conclusion Our results indicate that fetal intrauterine distress reduce the hyperphosphorylation of protein Tau in neonatal rats though up -regulating the content of glutamate.GSK-3βis the key protein in this signaling pathway.