術(shù)后認(rèn)知功能障礙老年小鼠海馬內(nèi)NogoA-NgR1通路的變化
發(fā)布時(shí)間:2018-03-07 07:52
本文選題:術(shù)后認(rèn)知功能障礙 切入點(diǎn):老年小鼠 出處:《臨床麻醉學(xué)雜志》2017年05期 論文類型:期刊論文
【摘要】:目的觀察術(shù)后認(rèn)知功能障礙老年小鼠海馬內(nèi)神經(jīng)生長抑制因子NogoA及其受體NgR1表達(dá)的變化,并探討其可能機(jī)制。方法采用異氟醚麻醉+腹腔探查術(shù)建立POCD模型。老年雄性C57BL/6小鼠40只,隨機(jī)分為四組:O_2+Saline組(OS組)、O_2+NEP1-40組(ON組)、異氟醚麻醉+腹腔探查術(shù)+Saline組(SS組)及異氟醚麻醉+腹腔探查術(shù)+NEP1-40組(SN組),每組10只。麻醉前7d行右側(cè)腦室置管;麻醉前2h至行為學(xué)測試前2h每天側(cè)腦室注射NEP1-40(20μg/2μl)或等容的無菌生理鹽水,連續(xù)注射8d。術(shù)后第5天行曠場實(shí)驗(yàn),第6、7天分別行場景性和條件性恐懼實(shí)驗(yàn)訓(xùn)練和測試。行為學(xué)測試后2h,取小鼠海馬組織,采用Western blot法檢測NogoA、NgR1、RhoA、ROCK2和GAP43含量變化;Golgi染色檢測海馬CA1區(qū)神經(jīng)元樹突棘數(shù)量改變。結(jié)果與OS和ON組比較,SS組在場景性恐懼實(shí)驗(yàn)測試中僵直反應(yīng)百分比明顯降低,海馬內(nèi)NogoA、NgR1、RhoA和ROCK2含量明顯升高,GAP43含量和總的、新生的和成熟的樹突棘數(shù)量明顯減少(P0.05);與SS組比較,SN組在場景性恐懼實(shí)驗(yàn)測試中僵直反應(yīng)百分比明顯升高,海馬內(nèi)RhoA和ROCK2含量明顯降低,GAP43含量和總的、新生的和成熟的樹突棘數(shù)量明顯增多(P0.05)。結(jié)論麻醉手術(shù)致老年小鼠認(rèn)知功能損害與其海馬內(nèi)NogoA-NgR1通路過度激活有關(guān)。
[Abstract]:Objective to observe the expression of nerve growth inhibitor (NogoA) and its receptor (NgR1) in hippocampus of senile mice with cognitive impairment after operation. Methods the POCD model was established by isoflurane anesthesia and abdominal cavity exploration. 40 old male C57BL / 6 mice were used. The rats were randomly divided into four groups: group O _ 2: O _ 2 Saline group: OS group (n = 10), NEP1-40 group (n = 10), Saline group (SS group) and NEP1-40 group (n = 10). Right ventricular catheterization was performed 7 days before anesthesia (n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 7 days before anesthesia). Two hours before anesthesia and two hours before behavioral test, NEP1-40(20 渭 g / 2 渭 l or isovolumetric sterile saline was injected into the lateral ventricle every day for 8 days. The open field test was performed on the 5th day after operation. On the 6th and 7th day, the training and testing of scenario and conditioned fear were performed respectively. The hippocampal tissue of mice was taken at 2 hours after behavioral test. Western blot method was used to detect the changes of NgR1R1RhoAroCK2 and GAP43 content in hippocampal CA1 neurons. Results compared with OS and on groups, the percentage of stiffness in SS group was significantly lower than that in OS and on groups. The contents of NgR1 RhoA and ROCK2 in hippocampus increased significantly, and the total number of new and mature dendritic spine decreased significantly (P 0.05), and the percentage of stiffness in SNS group was significantly higher than that in SS group. The contents of RhoA and ROCK2 in hippocampus significantly decreased the content of GAP43 and the total number of new and mature dendritic spine increased significantly. Conclusion the cognitive impairment induced by anesthesia in aged mice is related to the excessive activation of NogoA-NgR1 pathway in hippocampus.
【作者單位】: 南京大學(xué)醫(yī)學(xué)院臨床學(xué)院南京軍區(qū)南京總醫(yī)院麻醉科;東南大學(xué)附屬中大醫(yī)院麻醉科;
【基金】:國家自然科學(xué)基金(81471105)
【分類號(hào)】:R614
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