黄芪总苷和人参皂苷降低缺血性脑卒中患者脑脊液中谷氨酸、磷酸化Tau-东南大学学报医学版

黄芪总苷和人参皂苷降低缺血性脑卒中患者脑脊液中谷氨酸、磷酸化Tau

作者：杜杰

单位：咸宁市中心医院湖北科技学院附属第一医院神经内科, 湖北咸宁 437100

分类号：R151

出版年·卷·期（页码）：2017·36·第五期（828-832）

摘要：

目的：通过观察黄芪总苷和人参皂苷对缺血性脑卒中诱发的缺血缺氧强应激后老年受试者谷氨酸浓度和Tau超磷酸化的影响，探讨两者对Tau超磷酸化的调节，并比较其作用途径，以期为改善缺血性脑卒中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：即缺血性脑卒中（无卒中、缺血性脑卒中）和药物（静脉注射生理盐水、人参皂苷、黄芪总苷）的所有组合。干预后取脑脊液，HPLC测Glu含量，Western-blotting测p-AT8^Ser202和GSK-3β^1H8含量。结果：缺血性脑卒中可增加脑脊液内谷氨酸的浓度（P<0.05）；黄芪总苷可降低缺血性脑卒中诱发的过度升高的谷氨酸浓度，且两者有相减效果（P<0.05）；而人参皂苷对脑脊液中谷氨酸的浓度无明显影响（P>0.05）。缺血性脑卒中可增加脑脊液内p-AT8^Ser202以及促进Tau超磷酸化的调控蛋白GSK-3β^1H8的表达（P<0.05）；黄芪总苷和人参皂苷可减缓脑脊液内p-AT8^Ser202及促进其磷酸化的GSK-3β^1H8表达上调（P<0.05）；两者效果相似且和缺血性脑卒中诱发的缺血缺氧强应激的影响呈相减效果（P<0.05）。结论：黄芪总苷和人参皂苷可降低缺血性脑卒中患者脑脊液中谷氨酸及磷酸化Tau浓度，缓解缺血性脑卒中诱发的缺血缺氧强应激。

Objective:To observe Astragalosides and N-methyl -D-aspartate receptor antagonists on the concentration of glutamate and the ultra phosphorylation of Tau in elderly subjects with ischemic stroke induced by ischemia and hypoxia stress and the regulation of phosphorylation of Tau, in order to improve the understanding ofthe mechanism of cognitive impairment induced by ischemic stroke. Methods:2*3 factorial design was used in the design of ischemic stroke (2 levels:no stroke, ischemic stroke) and drugs (3 levels of normal saline, ginsenoside and Astragalus). After the intervention, the cerebrospinal fluid, HPLC and Glu were measured, and the contents of p-AT8Ser202 and GSK-3 were measured by Western-blot. The content of 1H8 and were measured. Results:Ischemic stroke increased the concentration of glutamic acid in the cerebrospinal fluid (P<0.05). Astragalosides reduced ischemic stroke induced by excessive increase of glutamic acid concentration, and the effect of subtraction (P<0.05). While the concentration of ginsenoside did not significantly affect on the CSF glutamate (P<0.05). The expression of ischemic stroke could increased in the cerebrospinal fluid of p-AT8Ser202 and promote Tau phosphorylation in the regulation of protein GSK-3 β^1H8(P<0.05). Astragaloside and ginsenoside could reduce cerebrospinal fluid p-AT8Ser202 and promote GSK-3 β^1H8 phosphorylation (P<0.05). Both effects were similar, and the effects of ischemia hypoxia and stress on ischemic stroke were subtracted (P<0.05). Conclusion:Total saponins of Astragalus and Panax ginseng saponins can improve the cognitive impairment in elderly patients with ischemic stroke by decreasing the concentration of glutamic acid and slowing down the Tau phosphorylation. Thus, it can alleviate the ischemic hypoxia and stress caused by ischemic stroke.

参考文献：

[1] 林也容,周龙,吴芳芳,等.急性胎兔缺血性脑卒中模型脑NO、iNOS和T-SOD变化试验研究[J].中国实用医药,2013,8(36):4-6.
[2] 吴希珠,郑晓春,陈小琳,等.母体肢体缺血预处理对缺血性脑卒中胎鼠复氧后脑脊液神经元凋亡的影响[J].中国病理生理杂志,2014,30(4):729-732,750.
[3] 林也容,林进皇,吴芳芳,等.急性胎兔缺血性脑卒中模型脑组织病理及NMDArl表达试验研究[J].中国医药科学,2013,3(23):38-41.
[4] 张华,卢敏,漆洪波,等.2脱氧葡萄糖诱导葡萄糖调节蛋白78表达上调对缺血性脑卒中胎鼠脑神经元的保护作用[J].中华妇产科杂志,2008,43(5):356-360.
[5] SINGH M,KAMAL YT,KHAN M A,et al.Matrix solid-Phase dispersion extraction and quantification of alpinetin in amomum seed using validated HPLC and HPTLC methods[J].Indian J Pharm Sci,2015,77(1):49-54.
[6] GUO C,YIN Y,DUAN J,et al.Neuroprotective effect and underlying mechanism of sodium danshensu[3-(3,4-dihydroxyphenyl) lactic acid from Radix and Rhizoma Salviae miltiorrhizae=Danshen] against cerebral ischemia and reperfusion injury in rats[J].Phytomedicine,2015,22(2):283-289.
[7] KEELEY R J,HONG NS,FISHER A,et al.Co-morbid beta-amyloid toxicity and stroke produce impairments in an ambiguous context task in rats without any impairment in spatial working memory[J].Neurobiol Learn Mem,2015,119(1):42-51.
[8] KANAMARU T,KAMIMURA N,YOKOTA T,et al.Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer's disease[J].Neurosci Lett,2015,587(12):126-131.
[9] EGLI S C,HIRNI D I,TAYLOR K I,et al.Varying strength of cognitive markers and biomarkers to predict conversion and cognitive decline in an early-stage-enriched mild cognitive impairment sample[J].J Alzheimers Dis,2015,44(2):625-633.
[10] WANG B,TANAKA K,JI B,et al.Low-dose total-body carbon-ion irradiations induce early transcriptional alteration without late Alzheimer's disease-like pathogenesis and memory impairment in mice[J].J Neurosci Res,2014,92(7):915-926.
[11] GUO L,HE P,NO Y R,et al.Krüppel-like factor 5 incorporates into the β-catenin/TCF complex in response to LPA in colon cancer cells[J].Cell Signal,2015,27(5):961-968.
[12] KETTUNEN P,LARSSON S,HOLMGREN S,et al.Genetic variants of GSK3B are associated with biomarkers for Alzheimer's disease and cognitive function[J].J Alzheimers Dis,2015,44(4):1313-1322.
[13] DESAI S S,MODALI S D,PAREKH V I,et al.GSK-3β protein phosphorylates and stabilizes HLXB9 protein in insulinoma cells to form a targetable mechanism of controlling insulinoma cell proliferation[J].J Biol Chem,2014,289(9):5386-5398.
[14] SOKOLOSKY M,CHAPPELL W H,STADELMAN K,et al.Inhibition of GSK-3β activity can result in drug and hormonal resistance and alter sensitivity to targeted therapy in MCF-7 breast cancer cells[J].Cell Cycle,2014,13(5):820-833.
[15] TYAGARAJAN S K,GHOSH H,YEVENES G E,et al.Extracellular signal-regulated kinase and glycogen synthase kinase 3β regulate gephyrin postsynaptic aggregation and GABAergic synaptic function in a calpain-dependent mechanism[J].J Biol Chem,2013,288(14):9634-9647.
[16] MOORE S F,van den BOSCH M T,HUNTER R W,et al.Dual regulation of glycogen synthase kinase 3(GSK3)α/β by protein kinase C (PKC)α and Akt promotes thrombin-mediated integrin αⅡbβ3 activation and granule secretion in platelets[J].J Biol Chem,2013,288(6):3918-3928.
[17] NIE H,XUE X,LI J,et al.Nitro-oleic acid attenuates OGD/R-triggered apoptosis in renal tubular cells via inhibition of Bax mitochondrial translocation in a PPAR-γ-dependent manner[J].Cell Physiol Biochem,2015,35(3):1201-1218.
[18] IHARA M,ASANUMA H,YAMAZAKI S,et al.An interaction between GLP-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia/reperfusion injury[J].Am J Physiol Heart Circ Physiol,2015,308(10):H1287-297.
[19] YE Z,XIA P,CHENG Z G,et al.Neuroprotection induced by sevoflurane-delayed post-conditioning is attributable to increased phosphorylation of mitochondrial GSK-3β through the PI3K/Akt survival pathway[J].J Neurol Sci,2015,348(1-2):216-225.
[20] ZHANG P,LI S,GAO Y,et al.Novel benzothiazinones (BTOs) as allosteric modulator or substrate competitive inhibitor of glycogen synthase kinase 3β (GSK-3β) with cellular activity of promoting glucose uptake[J].Bioorg Med Chem Lett,2014,24(24):5639-5643.
[21] 梅涛,王蕾,徐立新,等.经颅多普勒早期预警动脉瘤性蛛网膜下腔出血致延迟性脑缺血[J].国际神经病学神经外科学杂志,2016,43(5):396-398.
[22] 殷俊,李艳冰,沈琴,等.ERK和CREB磷酸化在硫氢化钠对大鼠脑缺血再灌注神经保护的机制探讨[J].国际神经病学神经外科学杂志,2015,42(3):223-229.

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