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目的:评价维生素Kn 2对七氟烷致老龄小鼠认知功能降低的影响。n 方法:SPF级健康雌性C57BL/6J小鼠72只,12月龄,体重20~25 g,采用随机数字表法分为4组(n n=18):对照+玉米油组(Con+Oil组)、七氟烷+玉米油组(Sevo+Oil组)、对照+维生素Kn 2组(Con+Kn 2组)和七氟烷+维生素Kn 2组(Sevo+Kn 2组)。Sevo+Oil组和Sevo+Kn 2组小鼠给予2.5%七氟烷+33%氧气麻醉2 h。Con+Oil组和Con+Kn 2组小鼠只给予33%氧气处理。Con+Oil组和Sevo+Oil组小鼠在吸入氧气或七氟烷前30 min,腹腔注射玉米油100 μl;Con+Kn 2组和Sevo+Kn 2组腹腔注射维生素Kn 2(溶于玉米油浓度为1 mg/ml)100 mg/kg。吸入七氟烷后24 h时每组随机取8只小鼠处死取海马组织,采用ELISA法测定ATP酶活性、IL-1β、IL-6和TNF-α的含量,采用Western blot法检测AT8和PHF1的表达;每组余10只小鼠进行标准化饲养,吸入七氟烷后1、3、5、7和14 d时采用Y迷宫实验检测认知功能。n 结果:与Con+Oil组比较,Sevo+Oil组海马IL-1β、IL-6、TNF-α含量、AT8和PHF1表达水平升高,ATP酶活性降低,吸入七氟烷后1、3、5、7和14 d时自发交替百分比下降(n P<0.05);与Sevo+Oil组比较,Sevo+Kn 2组海马IL-1β、IL-6、TNF-α含量、AT8和PHF1表达水平降低,ATP酶活性升高,麻醉结束后1、3、5、7和14 d时自发交替百分比升高(n P0.05)。n 结论:维生素Kn 2可改善七氟烷致老龄小鼠认知功能降低,其机制与升高海马ATP酶活性,抑制AT8和PHF1表达上调有关。n “,”Objective:To evaluate the effects of vitamin Kn 2 on sevoflurane-induced cognitive decline in aged mice.n Methods:A total of 72 SPF healthy female C57BL/6J mice, aged 12 months, weighing 20-25 g, were divided into 4 groups (n n=18 each) using a random number table method: control+ corn oil group (group Con+ Oil), sevoflurane+ corn oil group (group Sevo+ Oil), control+ vitamin Kn 2 group (group Con+ Kn 2) and sevoflurane+ vitamin Kn 2 group (group Sevo+ Kn 2). The mice in Sevo+ Oil and Sevo+ Kn 2 groups were anesthetized with 2.5% sevoflurane+ 33% oxygen for 2 h. The mice in Con+ Oil and Con+ Kn 2 groups were treated with 33% oxygen only.The animals in Con+ Oil and Sevo+ Oil groups were intraperitoneally injected with corn oil 100 μl at 30 min before oxygen or sevoflurane inhalation.Vitamin K n 2 (dissolved in corn oil, concentration 1 mg/ml) 100 mg/kg was injected intraperitoneally in Con+ Kn 2 and Sevo+ Kn 2 groups.At 24 h after sevoflurane inhalation, 8 mice from each group were randomly selected and sacrificed, and the hippocampal tissues were removed for determination of activity of ATPase, contents of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and the expression of AT8 and PHF1 (by Western blot). The remaining 10 mice in each group received standardized feeding, and the cognitive function was assessed using Y-maze at 1, 3, 5, 7 and 14 days after sevoflurane inhalation.n Results:Compared with group Con+ Oil, the contents of IL-1β, IL-6 and TNF-α were significantly increased, expression of AT8 and PHF1 were up-regulated, activity of ATPase was decreased, and spontaneous alternation percentage was decreased at 1, 3, 5, 7 and 14 days after sevoflurane inhalation in group Sevo+ Oil (n P<0.05). Compared with group Sevo+ Oil, the contents of IL-1β, IL-6 and TNF-α were significantly decreased, expression of AT8 and PHF1 were down-regulated, activity of ATPase was increased, and spontaneous alternation percentage was increased at 1, 3, 5, 7 and 14 days in group Sevo+ Kn 2 (n P0.05).n Conclusion:Vitamin Kn 2 can improve sevoflurane-induced cognitive decline in aged mice, the mechanism is related to increasing activity of ATPase and inhibiting the up-regulation of AT8 and PHF1 expression in hippocampus.n