国际麻醉学与复苏杂志   2017, Issue (5): 0-0
    
人参皂苷Rg1对七氟醚麻醉所致幼鼠远期认知功能障碍的保护作用及机制
缪慧慧, 洪方晓, 丁冠男, 张晔, 田鸣1()
1.首都医科大学附属北京友谊医院
Effects of ginsenoside Rg1 on sevoflurane anesthesia induced long-term cognitive dysfunction in neonatal mice
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摘要:

目的  观察人参皂苷Rg1(ginsenoside Rg1, Rg1)对七氟醚麻醉所致幼鼠远期认知功能障碍的改善作用及其机制。 方法 72只新生6日龄C57BL/6J小鼠采用随机数字表法分为4组(每组18只):对照+生理盐水组(Con+NS组)、对照+Rg1组(Con+Rg1组)、七氟醚麻醉+生理盐水组(Sev+NS组)、七氟醚麻醉+Rg1组(Sev+Rg1组)。Sev+NS组和Sev+Rg1组分别在出生后6~8 d每天接受3%七氟醚+100%氧气麻醉2 h,Con+NS组及Con+Rg1组小鼠在相应日龄吸入相同时间100%氧气。麻醉前30 min各组分别进行生理盐水(1 ml·kg-1·d-1)或 Rg1(10 mg ·kg-1·d-1)腹腔注射。各组取12只小鼠于第31~37天行水迷宫实验,行为学测试结束后取海马行Western blot检测突触后密度蛋白95(postsynaptic density 95, PSD-95)含量,其余小鼠(每组6只)于第8天麻醉手术后即刻行ELISA检测海马ATP及活性氧簇(reactive oxygen species, ROS)水平。 结果 与Con+NS组比较,Sev+NS组第35~37天水迷宫实验逃避潜伏期[(35.6±4.5)、(28.3±3.5)、(21.9±2.4) s比(45.7±8.1)、(41.9±8.8)、(35.1±12.4) s]明显延长(P<0.05),平台次数[4(8,2)次比2(6,0)次]明显减少(P<0.05),PSD-95水平[(100±6)%比(77±6)%]明显降低(P<0.05),ROS水平[(100±4)%比(121±11)%]明显升高(P<0.05),ATP水平[(100±6)%比(82±7)%]明显降低(P<0.05)。Sev+Rg1组与Con+Rg1组比较,31~37 d水迷宫实验逃避潜伏期、穿越平台次数、PSD-95水平、ROS水平及ATP水平差异均无统计学意义(P>0.05)。 结论 Rg1可改善七氟醚麻醉所致的幼鼠远期认知功能障碍,其机制可能与抑制氧化应激保护线粒体功能并增强突触可塑性有关。

关键词: 人参皂苷Rg1; 认知功能障碍; 七氟醚; 幼鼠
Abstract:

Objective Observing the effects of ginsenoside Rg1(Rg1) on sevoflurane anesthesia induced cognitive dysfunction in neonatal mice. Methods Seventy two C57BL/6J mice at postnatal day 6 were randomly divided into the following four groups(n=18) according to the random number table: control with normal saline(NS) group(Con+NS group), control with Rg1 group (Con+Rg1 group), sevoflurane anesthesia with NS group (Sev+NS group) and sevoflurane anesthesia with Rg1 group (Sev+Rg1 group). The mice were subjected to 3% sevoflurane plus 100% O2 or 100% O2 2 h daily for 3 consecutive days, respectively. The mice in different groups were given intraperitoneal injections of NS (1 ml·kg-1·d-1) or Rg1 (10 mg·kg-1·d-1) half an hour before anesthesia, respectively. The Morris Water Maze test was performed at postnatal day 31-37 with 12 mice in each group. The hippocampus tissue was collected after the behavioral test to measure the expression level of postsynaptic density 95 protein (PSD-95). ELISA was used to test the ATP and reactive oxygen species(ROS) levels in the hippocampus immediately after the last anesthesia at day 8 with 6 mice in each group. Results Compared with the Con+NS group[(35.6±4.5), (28.3±3.5), (21.9±2.4) s], the escape latency in morris water maze test of Sev+NS group at postnatal day 35-37 were increased significantly[(45.7±8.1), (41.9±8.8), (35.1±12.4) s](P<0.05). Compared with the Con+NS group 4(8, 2), times across the platform in morris water maze test of Sev+NS group were decreased significantly 2(6, 0)(P<0.05). Compared with the Con+NS group [(100±6)%] (P<0.05), the expression level of PSD-95 of Sev+NS group [(77±6) %] were decreased significantly. Compared with the Con+NS group[(100±4)%], the ROS level of Sev+NS group[(121±11)%] were increased significantly(P<0.05). Compared with the Con+NS group[(100±6)%], the ATP levels of Sev+NS group[(82±7)%] were decreased significantly(P<0.05). In addition, for Sev+Rg1 group, the escape latency and times across the platform in morris water maze test, the content of PSD-95, the ROS and ATP levels were not significantly different with Con+Rg1 group(P>0.05). Conclusions Rg1 can alleviate sevoflurane anesthesia induced hippocampus-dependent long-term cognitive dysfunction in neonatal mice, which is associated with the oxidative stress, mitochondrial dysfunction and synaptic plasticity in hippocampus.

Key words: Ginsenoside Rg1; Cognitive dysfunction; Sevoflurane; Neonatal mice