黄芪总苷和MK-801对宫内窘迫后认知障碍的作用

目的：研究黄芪总苷和地卓西平马来酸（MK-801）对宫内窘迫后的缺氧后新生鼠的Tau蛋白磷酸化程度的影响。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：生理盐水、MK-801、黄芪总苷）的所有组合。新生鼠生长至12周时留取海马，高效液相色谱（HPLC）检测谷氨酸（Glu）含量，IHC-SP检测p-AT8^Ser202与GSK-3β^1H8表达。结果：黄芪总苷可降低宫内窘迫诱发的Glu浓度升高；MK-801对海马中Glu的浓度无明显影响。宫内窘迫可增加海马内磷酸化程度的Tau蛋白p-AT8^Ser202以及促进Tau蛋白磷酸化程度的调控蛋白GSK-3β^1H8的表达；黄芪总苷和MK-801可减缓p-AT8^Ser202磷酸化程度。结论：黄芪总苷可以通过降低海马Glu浓度减缓Tau蛋白的磷酸化；GSK-3β是该信号通路的关键蛋白；黄芪总苷改善由于宫内窘迫诱发导致缺氧后的学习记忆能力低下的效果优于MK-801。

Effects of astragalosides and NMDA receptor antagonist against the impairment of learning memory after the fetal intrauterine distress in neonatal rats

OBJECTIVE To observe the effects of total glucosides of Astragalus on the phosphorylation of Tau protein in neonatal rats after intrauterine distress.METHODS The 2×3 factorial design: fetal distress (2 levels: no disposition, implementation of fetal distress in clamping uterine artery of pregnant rats 2/3 closed for 10min) and drugs (3 levels: normal saline, MK-801, Astragalosides) for all combinations. Neonatal rats were fed to 12 weeks and Glu was detected by HPLC. P-AT8^Ser202 and GSK-3β^1H8 expressions were detected by IHC-SP.RESULTS Astragalosides decreased the Glu concentration induced by intrauterine distress, and MK-801 had no significant effect on the concentration of Glu in hippocampus. Fetal hippocampus increased the phosphorylation level of Tau protein p-AT8^Ser202 and promoted expression of Tau protein phosphorylation of the regulatory protein GSK-3β^1H8. Astragalosides and MK-801 reduced the phosphorylation level of p-AT8^Ser202.CONCLUSION Our results indicate that fetal intrauterine distress reduce the hyperphosphorylation of protein Tau in neonatal rats though upregulating the content of glutamate.