Objective To discuss the influence of subanesthesia,sedation and anesthesia doses of Propofol on learning and memory functions,hippocampal tissues in rats with hyperlipidemia.Methods Totally 65 healthy adult male SD rats were randomly divided into basic diet group (15 rats) and high-fat diet group (50 rats).After 6 weeks of feeding,10 rats were used for measurement of blood lipids.The 40 rats of successful model were randomly divided into 4 groups.Group A had intraperitoneal injection of saline 75 mg/kg;groups B,C and D were anesthetized by intraperitoneal injection of subanesthetic (10 mg/kg),sedation (30 mg/kg) and anesthetic (375 mg/kg)doses of 1％ Propofol for 5 consecutive days.Morris water maze training was carried out and spatial memory was measured 20 min and 6-7 days after drug administration.On the 8th day after the first administration,the hippocampal tissues were obtained to measure the level of Tau protein phosphorylation,caspase-3 expression level and γ-amino butyric acid (GABA) level.Results With the increase of the days of drug administration and training,the escape latency was significantly shortened in the 4 groups (P ＜ 0.05).The escape latency in the groups C and D at different time points was significantly longer than that in the groups A and B (P ＜ 0.05),and the escape latency in the group D was significantly longer than that in the group C (P ＜ 0.05).In the search space experiments on the 7th day,the platform-crossing times of the groups C and D were significantly fewer than those of the group A and B (P ＜ 0.05),and the platform-crossing times of the group D were significantly fewer than those of the group C (P ＜ 0.05);the GABA content of the hippocampal tissues and the average optical density of positive cells were significantly higher in the groups C and D than in the groups A and B (P ＜ 0.05),and significantly higher in the group D than in the group C (P ＜ 0.05).Conclusions Sedation and anesthesia doses of Propofol can reduce the spatial memory in hyperlipidemia rats,which may be associated with high levels of GABA in hippocampus and Tau proteinhyperphosphorylation.%目的 探讨亚麻醉、镇静及麻醉剂量丙泊酚对高脂血症大鼠的空间记忆及海马组织的影响.方法 65只健康成年雄性SD大鼠随机分为基础性喂养组(15只)和高脂饲料喂养组(50只),喂养6周后随即抽取10只测定血脂.将复制模型成功的40只大鼠随机分为4组:A组腹腔注射生理盐水75 mg/kg;B、C、D组分别腹腔注射亚麻醉(10mg/kg)、镇静(30mg/kg)及麻醉剂量(375mg/kg)丙泊酚(浓度为1％),连续给药5d,给药后20 min以及第6～7天均进行Morris水迷宫训练,测定空间记忆能力;给药后第8天,断头取脑,获得海马组织,测定其中Tau蛋白磷酸化水平、Caspase-3表达水平和y氨基丁酸(GABA)水平.结果 随着给药和训练天数增加,4组大鼠的逃避潜伏期缩短(P＜0.05);C组和D组大鼠不同时间点的逃避潜伏期高于A组和B组(P＜()05),且D组高于C组(P＜0.05);第7天空间搜索实验时,C组和D组大鼠穿越平台次数低于A组和B组(P＜0.05),且D组低于C组(P＜0.05);C组和D组大鼠海马组织中GABA含量、阳性细胞平均光密度值高于A组和B组(P＜0.05),且D组高于C组(P＜0.05).结论 镇静和麻醉剂量的丙泊酚会降低高脂血症大鼠的空间记忆能力,可能与海马组织中GABA的高水平和Tau蛋白过度磷酸化有关.
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