目的 探討油酰乙醇胺對東莨菪堿誘導(dǎo)小鼠認(rèn)知功能損傷的保護(hù)作用。方法 將小鼠隨機(jī)分為6組：對照組、模型組、多奈哌奇組（陽性藥，3 mg·kg^-1）和油酰乙醇胺低、中、高劑量（50、100、200 mg·kg^-1）組，每組6只。在ig給藥4周后，除對照組外，各組ip 3 mg·kg^-1的東莨菪堿建立阿爾茨海默病（AD）模型。避暗、跳臺(tái)行為學(xué)實(shí)驗(yàn)檢測小鼠記憶功能； ELISA法檢測小鼠海馬和大腦皮層中乙酰膽堿（Ach）和乙酰膽堿酯酶（AChE）水平；HE染色觀察小鼠大腦皮層及海馬損傷。結(jié)果 與對照組比較，模型組的避暗潛伏期顯著縮短、避暗錯(cuò)誤次數(shù)顯著增加（P<0.001）；大腦皮層、海馬的Ach水平顯著減少（P<0.01、0.001），AChE活性顯著升高（P<0.001）；模型組的小鼠腦組織形態(tài)結(jié)構(gòu)不均勻，組織細(xì)胞呈彌散狀，提示組織存在病變。與模型組比較，各給藥組的避暗潛伏期顯著升高、避暗錯(cuò)誤次數(shù)顯著減少（P<0.01）；油酰乙醇胺給藥組的小鼠大腦皮層、海馬組織Ach水平顯著升高（P<0.05、0.01），AChE活性顯著降低（P<0.01、0.001）；小鼠腦組織形態(tài)結(jié)構(gòu)病理改變減輕。結(jié)論 油酰乙醇胺對東莨菪堿誘導(dǎo)學(xué)習(xí)記憶障礙模型小鼠的認(rèn)知功能具有改善作用，其作用機(jī)制可能與調(diào)節(jié)膽堿能系統(tǒng)功能、促進(jìn)神經(jīng)細(xì)胞存活有關(guān)。

Objectives To explore the protective effect of N-oleoylethanolamine alleviates scopolamine-induced spatial learning and memory deficits in mice. Methods The mice were randomly divided into six groups:control group, model group, donepezil group (positive drug, 3 mg·kg^-1) and N-oleoylethanolamine low, medium and high dose (50, 100, 200 mg·kg^-1) groups, with six mice in each group. Four weeks after ig administration, except for the control group, dementia models were established by ip 3 mg·kg^-1 of scopolamine in each group. Test the memory function of mice through behavioral experiments of avoiding darkness and jumping platforms. The levels of acetylcholine (Ach) and acetylcholinesterase (AChE) in hippocampus and cerebral cortex of mice were detected by ELISA. HE staining was used to observe the damage to the cerebral cortex and hippocampus of mice. Results Compared with the control group, the model group had a significantly shorter latency and an increased number of avoidance errors (P < 0.001), the levels of Ach in the cerebral cortex and hippocampus were significantly reduced (P < 0.01, 0.001), while the activity of AChE was significantly increased (P < 0.001), the brain tissue morphology and structure of the model group mice were uneven, with diffuse tissue cells, indicating the presence of pathological changes in the tissue. Compared with model group, the latency of dark avoidance significantly increased and the number of dark avoidance errors significantly decreased in each medication group (P < 0.01), Ach level in cerebral cortex and hippocampus of mice in N-oleoylethanolamine administration group was significantly increased (P < 0.05, 0.01), and AChE activity was significantly reduced (P < 0.01, 0.001), and the pathological changes in the morphology and structure of mouse brain tissue were alleviated. Conclusion N-oleoylethanolamine can improve the cognitive function of scopolamine-induced learning and memory impairment model mice. The effect of N-oleoylethanolamine may be related to regulating the function of the cholinergic system and promoting the survival of nerve cells.

R965

福建省科技廳自然科學(xué)基金面上項(xiàng)目（2021J01344）