米诺环素通过抑制炎症因子和谷氨酸转运体表达减轻缺氧所致新生鼠认知损伤

发布时间：2018-02-27 22:28

本文关键词： 米诺环素缺氧炎症反应谷氨酸转运体 Tau蛋白过度磷酸化认知功能　出处：《生理学报》2016年02期 　论文类型：期刊论文

【摘要】：本研究旨在探讨米诺环素(minocycline)对新生大鼠缺氧后认知功能的影响及其可能的作用机制。取出生后1 d的Sprague Dawley(SD)大鼠,经系统性缺氧,构建缺氧性脑损伤(hypoxic brain damage,HBD)模型。缺氧结束后2 h,腹腔注射生理盐水(Hy组)或米诺环素(Hy+M组),未造模的同龄大鼠为正常对照组(NG组)。各组大鼠出生后第30天用Y臂电子迷宫检测学习、记忆能力;缺氧后7 d用Western blot检测大鼠海马组织炎症介质(Iba-1、IL-1β、TNF-α和TGF-β1)、谷氨酸转运体(EAAT1和EAAT2)、总Tau及不同位点(Tyr18、Thr205、Thr231、Ser396和Ser404)磷酸化Tau蛋白的表达情况。结果显示,缺氧后大鼠学习、记忆能力显著下降,米诺环素处理后能改善其学习、记忆能力。缺氧后7 d,大鼠海马组织Iba-1、IL-1β、TNF-α、EAAT2和T231位点磷酸化的Tau蛋白表达升高,总Tau蛋白的表达下降;米诺环素处理后能降低缺氧后大鼠海马组织Iba-1、IL-1β、TNF-α和EAAT2的表达水平,但不能干预总Tau及磷酸化Tau蛋白的表达。以上结果提示,米诺环素能改善缺氧后大鼠认知功能障碍,其保护机制可能与其对脑内炎症反应和功能异常的谷氨酸转运体的抑制有关,但不涉及对Tau蛋白异常过度磷酸化的调节。
[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- 伪 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- 伪 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.
【作者单位】：昆明医科大学病理学与病理生理学系;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)
【分类号】：R749.1

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