目的 探討七氟醚的麻醉時間對大鼠認(rèn)知功能及海馬內(nèi)乙酰膽堿酯酶（AChE）活性和β-淀粉樣蛋白（Aβ_1-42）含量的影響。方法 隨機(jī)將120只成年SD大鼠分為七氟醚2、4、6 h組和對照組，每組30只。七氟醚2、4、6 h組分別給予3%七氟醚2、4、6 h，對照組吸入空氣。麻醉完成后1、3、7 d行Morris水迷宮實驗和曠場實驗，記錄逃避潛伏期、穿越平臺次數(shù)、第3象限活動時間、中央格停留時間、2 min穿越格子數(shù)。實驗結(jié)束后處死大鼠取海馬組織標(biāo)本，用比色法測定AChE活性、酶聯(lián)免疫吸附試驗測定Aβ_1-42含量。結(jié)果 七氟醚組逃避潛伏期較對照組顯著延長（P<0.05），第3象限活動時間、穿越平臺次數(shù)較對照組顯著減少（P<0.05）；七氟醚2、4 h組中央格停留時間、2 min內(nèi)穿越格子數(shù)與對照組無統(tǒng)計學(xué)差異，七氟醚6 h組中央格停留時間顯著大于對照組（P<0.05），2 min內(nèi)穿越格子數(shù)顯著小于對照組（P<0.05），且變化程度均與七氟醚吸入時長呈正相關(guān)性。七氟醚組海馬AChE活性、Aβ_1-42含量顯著高于對照組（P<0.05），且隨七氟醚吸入時間的延長而升高。結(jié)論 七氟醚麻醉可導(dǎo)致大鼠認(rèn)知功能損傷，且損傷程度隨麻醉時間延長而加重，其機(jī)制可能與七氟醚上調(diào)海馬AChE活性、促進(jìn)Aβ_1-42生成有關(guān)。

Objective To investigate the effects of sevoflurane anesthesia time on cognitive function and acetylcholinesterase (AChE) and β-amyloid protein (Aβ_1-42) in hippocampus of rats. Methods 120 adult SD rats were randomly divided into sevoflurane 2, 4 and 6 h groups and control group, 30 rats in each group. Sevoflurane 2, 4 and 6 h groups were given 3% sevoflurane for 2 h, 4 h and 6 h respectively, while the control group was inhaled air. Morris water maze test and open field test were performed 1, 3 and 7 days after anesthesia. The escape latency, the number of platform crossings, the activity time of the third quadrant, the residence time of the central grid and the number of grid crossings in 2 minutes were recorded. At the end of the experiment, rats were killed and hippocampal tissue samples were taken. AChE activity was measured by colorimetry, and the content of Aβ_1-42 was determined by enzyme-linked immunosorbent assay. Results The escape latency of sevoflurane experimental group was longer than that of control group (P < 0.05). The activity time of the third quadrant and the number of platform crossings were less than that of control group (P < 0.05). The escape latency decreased with the prolongation of sevoflurane inhalation time. The activity time of the third quadrant and the number of platform crossings were increased with the prolongation of sevoflurane inhalation time (P < 0.05). There was no significant difference in the residence time of the central grid and the number of grid crossings in 2 minutes between sevoflurane 2 and 4 h groups and control group. The residence time of the central grid in sevoflurane 6 h group was longer than that in control group (P < 0.05), and the number of grid crossings in 2 minutes was less than that in control group (P < 0.05). The activity of AChE and the content of Aβ_1-42 in hippocampus of sevoflurane group were higher than those of control group (P < 0.05), and increased with the prolongation of sevoflurane inhalation time. Conclusion Sevoflurane anesthesia can lead to cognitive impairment in rats, and the degree of impairment is aggravated with the prolongation of anesthesia time. The mechanism may be related to sevoflurane upregulating AChE activity and promoting the production of Aβ_1-42 in hippocampus.

R965

河南省科技發(fā)展計劃項目（152300410163）