本文關(guān)鍵詞： 米諾環(huán)素 缺氧 炎癥反應(yīng) 谷氨酸轉(zhuǎn)運體 Tau蛋白 過度磷酸化 認知功能　出處：《生理學(xué)報》2016年02期 　論文類型：期刊論文

【摘要】：本研究旨在探討米諾環(huán)素(minocycline)對新生大鼠缺氧后認知功能的影響及其可能的作用機制。取出生后1 d的Sprague Dawley(SD)大鼠,經(jīng)系統(tǒng)性缺氧,構(gòu)建缺氧性腦損傷(hypoxic brain damage,HBD)模型。缺氧結(jié)束后2 h,腹腔注射生理鹽水(Hy組)或米諾環(huán)素(Hy+M組),未造模的同齡大鼠為正常對照組(NG組)。各組大鼠出生后第30天用Y臂電子迷宮檢測學(xué)習(xí)、記憶能力;缺氧后7 d用Western blot檢測大鼠海馬組織炎癥介質(zhì)(Iba-1、IL-1β、TNF-α和TGF-β1)、谷氨酸轉(zhuǎn)運體(EAAT1和EAAT2)、總Tau及不同位點(Tyr18、Thr205、Thr231、Ser396和Ser404)磷酸化Tau蛋白的表達情況。結(jié)果顯示,缺氧后大鼠學(xué)習(xí)、記憶能力顯著下降,米諾環(huán)素處理后能改善其學(xué)習(xí)、記憶能力。缺氧后7 d,大鼠海馬組織Iba-1、IL-1β、TNF-α、EAAT2和T231位點磷酸化的Tau蛋白表達升高,總Tau蛋白的表達下降;米諾環(huán)素處理后能降低缺氧后大鼠海馬組織Iba-1、IL-1β、TNF-α和EAAT2的表達水平,但不能干預(yù)總Tau及磷酸化Tau蛋白的表達。以上結(jié)果提示,米諾環(huán)素能改善缺氧后大鼠認知功能障礙,其保護機制可能與其對腦內(nèi)炎癥反應(yīng)和功能異常的谷氨酸轉(zhuǎn)運體的抑制有關(guān),但不涉及對Tau蛋白異常過度磷酸化的調(diào)節(jié)。
[Abstract]:The aim of this study was to investigate the effect of minocycline on cognitive function after hypoxia in neonatal rats and its possible mechanism. The model of hypoxic brain damage (HBD) was established. 2 hours after hypoxia, normal saline Hy group was injected intraperitoneally, or minocycline Hy M group was injected intraperitoneally. The rats of the same age without model were treated with Y on the 30th day after birth. Arm electronic maze detection learning, The expression of TNF- 偽 and TGF- 尾 1, glutamate transporter, EAAT1 and EAAT2, total Tau and the phosphorylated Tau protein at different sites of Tyr18Thr205Tr231Ser396 and Ser404 were detected by Western blot on the 7th day after hypoxia. Memory ability decreased significantly, minocycline treatment improved its learning and memory ability. 7 days after hypoxia, the expression of phosphorylated Tau protein at Iba-1, IL-1 尾 and T231 sites in hippocampus of rats increased, while the expression of total Tau protein decreased. Minocycline treatment could decrease the expression of Iba-1 and IL-1 尾 -TNF- 偽 and EAAT2, but could not interfere with the expression of total Tau and phosphorylated Tau protein. These results suggest that minocycline can improve the cognitive function of rats after hypoxia. Its protective mechanism may be related to its inhibition of inflammatory response and abnormal glutamate transporter in brain, but it does not involve the regulation of abnormal phosphorylation of Tau protein.
【作者單位】： 昆明醫(yī)科大學(xué)病理學(xué)與病理生理學(xué)系;Department
【基金】：supported by the National Natural Science Foundation of China(No.81200939 and 31260242) the Fund of the Key Laboratory of Stem Cells and Regenerative Medicine of Yunnan Province,China(No.fzy2015001) the Natural Science Foundation of Yunnan Province,China(No.2011FB060)
【分類號】：R749.1

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