【摘要】：目的觀察膽堿對(duì)脂多糖(LPS)誘導(dǎo)的中樞神經(jīng)系統(tǒng)(CNS)炎癥反應(yīng)及認(rèn)知損傷的影響,并對(duì)其作用機(jī)制進(jìn)行分析。方法采用側(cè)腦室注射LPS建立小鼠CNS炎癥模型,隨機(jī)分為生理鹽水對(duì)照組、LPS組、LPS+膽堿40 mg/kg組、膽堿40 mg/kg組4組。藥物干預(yù)組和藥物對(duì)照組膽堿預(yù)處理3 d,下午12、2和4 pm各1次腹腔注射,對(duì)照組和LPS組生理鹽水預(yù)處理3 d(時(shí)間次數(shù)同上),膽堿給藥貫穿整個(gè)實(shí)驗(yàn)。觀察小鼠自發(fā)活動(dòng),測(cè)定小鼠空間學(xué)習(xí)和記憶能力。檢測(cè)海馬齒狀回IBA-1蛋白表達(dá)情況,測(cè)定海馬TNF-α、IL-1β水平,分析海馬α7nAchR、MAPK p38蛋白和磷酸化p38蛋白表達(dá)情況。結(jié)果與對(duì)照組相比,LPS組小鼠在水迷宮測(cè)試中穿臺(tái)次數(shù)明顯減少(P0.05),膽堿預(yù)處理后穿臺(tái)次數(shù)顯著上升(P0.05);與對(duì)照組相比,LPS組小鼠海馬IBA-1蛋白(P0.0001)、TNF-α(P0.001)與IL-1β(P0.01)明顯升高,膽堿干預(yù)后明顯降低IBA-1蛋白(P0.05)和IL-1β(P0.05)的升高,部分抑制TNF-α的升高;LPS處理后p38MAPK磷酸化水平明顯升高(P0.05),膽堿預(yù)處理后顯著降低其磷酸化水平(P0.05);膽堿干預(yù)組α7nAchR表達(dá)與其他3組相比顯著增高(P0.05)。結(jié)論膽堿可能通過(guò)激活αnAchR來(lái)抑制LPS誘導(dǎo)的小鼠海馬p38MAPK磷酸化,對(duì)LPS誘導(dǎo)的CNS炎癥以及認(rèn)知功能障礙的小鼠具有保護(hù)效應(yīng)。
[Abstract]:Aim to observe the effect of choline on the inflammatory response and cognitive impairment of central nervous system (CNS) induced by lipopolysaccharide (LPS), and to analyze its mechanism. Methods the inflammatory model of CNS was established by intracerebroventricular injection of LPS in mice. The mice were randomly divided into four groups: normal saline control group, LPS 40 mg/kg group and choline 40 mg/kg group. The drug intervention group and the drug control group were pretreated with choline for 3 days, then injected intraperitoneally for 12 minutes and 4 pm respectively. The control group and the LPS group were pretreated with normal saline for 3 days (the time was the same). Choline administration ran through the whole experiment. The spontaneous activity of mice was observed and the ability of spatial learning and memory was measured. The expression of IBA-1 protein in dentate gyrus and the levels of TNF- 偽 and IL-1 尾 in hippocampus were detected, and the expression of 偽 7nAchRmMAPK p38 protein and phosphorylated p38 protein in hippocampus were analyzed. Results compared with the control group, the number of platform piercing was significantly decreased in LPS group (P0.05), and increased significantly after choline pretreatment (P0.05). Compared with the control group, IBA-1 protein (P0.0001), TNF- 偽 (P0.001) and IL-1 尾 (P0.01) were significantly increased in LPS group. The levels of IBA-1 protein (P0.05) and IL-1 尾 (P0.05) were significantly decreased after choline treatment, and the increase of TNF- 偽 was partly inhibited. After LPS treatment, p38MAPK phosphorylation level increased significantly (P0.05), choline pretreatment significantly decreased its phosphorylation level (P0.05); choline intervention group 偽 7nAchR expression was significantly higher than the other three groups (P0.05). Conclusion choline may inhibit p38MAPK phosphorylation in hippocampus of mice induced by LPS by activating 偽 nAchR, and has protective effect on CNS inflammation induced by LPS and cognitive impairment in mice.
【作者單位】： 解放軍總醫(yī)院麻醉手術(shù)中心;中國(guó)醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)學(xué)院;軍事醫(yī)學(xué)科學(xué)院衛(wèi)生學(xué)環(huán)境醫(yī)學(xué)研究所心血管藥物研究中心;
【基金】：軍隊(duì)保健專(zhuān)項(xiàng)課題(15BJZ36) 軍隊(duì)醫(yī)藥衛(wèi)生十二五重大專(zhuān)項(xiàng)課題(AWS11J003)
【分類(lèi)號(hào)】：R741
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本文編號(hào)：2294813