目的 探讨异氟醚对成年小鼠认知功能的影响及ERK磷酸化抑制在改善异氟醚致成年小鼠认知损害中的作用。方法 将66只2月龄C57BL/6J雄性小鼠随机分为3组:对照组(Con)、异氟醚组(Iso)、干预组(Iso+U0126),每组22只。Iso组和Iso+U0126组给予1.4%异氟醚+60%氧气+38.6%空气处理2 h;其中Iso+U0126组于异氟醚处理前30 min,给予100 mg/kg U0126腹腔注射预处理。Con组仅给予60%氧气+40%空气处理2 h。造模结束后采用ELISA检测各组小鼠皮层Aβ1-42水平,Western blot法和免疫荧光法测定各组小鼠皮层ERK1磷酸化水平,Morris水迷宫检测小鼠造模结束后1~7 d的认知功能改变。结果 与Con组比较,Iso组p-ERK1表达上调(0.35±0.02 vs. 0.17±0.03),Aβ1-42表达上调(66.5±4.2 vs. 43.7±5.1),小鼠逃避潜伏期显著延长(37.20±2.87 vs. 11.20±2.76),穿越平台次数明显减少(2.80±1.48 vs. 5.60±1.96),差异均有统计学意义(P<0.05)。与Iso组比较,Iso+ U0126组p-ERK1表达下调(0.25±0.05 vs. 0.35±0.02),小鼠逃避潜伏期缩短(15.30±4.76 vs. 37.20±2.87),穿越平台次数明显增加(5.30±2.58 vs. 2.80±1.48),差异均有统计学意义(P<0.05)。结论 1.4%异氟醚连续2 h处理可致小鼠认知功能损伤, ERK磷酸化抑制可改善异氟醚所致的认知损害。
Abstract
Objective To investigate the influence of isoflurane on cognitive function and the inhibitory effect of ERK phosphorylation on cognitive impairment induced by isoflurane in mice. Methods Sixty-six two-month-old C57BL/6J male mice were randomly divided into three groups: the control group (Con), isoflurane group (Iso), and Iso+U0126 group (IsoU). Mice in the Iso group and Iso + U0126 group were anesthetized by 1.4% isoflurane + 60% oxygen + 38.6% air for 2 hours, while those in the Con group inhaled 60% oxygen + 40% air alone for 2 hours. U0126 (100 mg/kg) was injected intraperitoneally into mice in the Iso+U0126 group before isoflurane treatment. After modeling, ELISA was used to detect the level of Aβ1-42 in the cortex of mice in each group. Western blot and immunofluorescence were used to determine the level of ERK1 phosphorylation in the cortex of these mice. The Morris water maze was used to detect the cognitive function of mice at day 1 to 7 after modeling. Results Compared with the Con group, the expression of p-ERK1 in the Iso group was up-regulated (0.35±0.02 vs. 0.17±0.03, P<0.05), so was the expression of Aβ1-42 (66.5±4.2 vs. 43.7±5.1, P<0.05), the escape latency was significantly prolonged (37.20±2.87 vs. 11.20±2.76), and the number of times the mice crossed the platforms was significantly reduced (2.80±1.48 vs. 5.60±1.96). Compared with the Iso group, the expression of p-ERK1 in the Iso+U0126 group was down-regulated (0.25±0.05 vs. 0.35±0.02, P<0.05), the escape latency was significantly shortened (15.30±4.76 vs. 37.20±2.87), and the number of times the mice crossed the platforms was significantly increased (5.30±2.58 vs. 2.80±1.48, P<0.05). Conclusions Two consecutive hours of exposure to 1.4% isoflurane can cause cognitive impairment in mice, and the inhibition by ERK phosphorylation can ameliorate cognitive impairment induced by isoflurane.
关键词
异氟醚 /
认知功能障碍 /
细胞外信号调节激酶
Key words
isoflurane /
cognitive impairment /
extracellular signal-regulated kinase
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