右美托咪定对七氟烷麻醉后老年小鼠认知功能障碍的影响

Effects of dexmedetomidine on cognitive dysfunction in aged mice after sevoflurane anesthesia

目的观察右美托咪定对七氟烷麻醉后老年小鼠认知功能障碍及海马组织磷酸化环腺苷酸应答元件结合蛋白(pCreb)、早期生长反应因子1(Egr1)表达的影响。方法昆明老年小鼠60只,随机分为对照组(n=20)、模型组(n=20)及实验组(n=20)。模型组与实验组小鼠均吸入3%七氟烷4 h,对照组吸入100%氧气4 h;其中实验组小鼠在吸入3%七氟烷前腹腔注射盐酸右美托咪定10μL;对照组与模型组腹腔注射0.9%氯化钠溶液10μL。用Morris水迷宫测试仪与旷场实验测定小鼠的认知功能;用免疫组化法与蛋白质印迹(Wb)法检测海马组织pCreb、Egr1蛋白表达。结果对照组、模型组及实验组小鼠第4天的逃逸潜伏期分别为(17.28±3.24),(27.73±5.92),(22.96±3.75)s;穿越原平台次数分别为(5.64±1.21),(2.97±0.72),(4.83±1.16)次;跨格次数分别为(90.21±18.02),(41.52±9.03),(73.64±17.11)次;直立次数分别为(11.63±3.37),(4.23±1.12),(8.56±1.54)次;中央格停留时间分别为(9.37±1.69),(32.83±7.65),(14.24±2.51)s。定位航行实验的第1~4天,3组小鼠的逃逸潜伏期均逐渐缩短,但模型组与实验组均明显长于对照组,实验组短于模型组,差异均有统计学意义(P<0.05);与对照组比较,模型组小鼠穿越原平台的次数、跨格次数与直立次数均明显减少,实验组多于模型组,差异均有统计学意义(均P<0.05);而中央格停留时间延长,实验组短于模型组,差异有统计学意义(P<0.05);模型组海马组织pCreb、Egr1蛋白阳性细胞百分比与相对表达量均明显低于对照组,而实验组高于模型组,差异均有统计学意义(均P<0.05)。结论右美托咪定可改善七氟烷麻醉后老年小鼠的认知功能,其作用机制可能与上调海马组织pCreb与Egr1蛋白表达相关。

Objective To investigate the effects of dexmedetomidine on cognitive dysfunction and expression of phosphorylated cyclic adenylate response element binding protein(pCreb) and early growth response factor 1(Egr1) in hippocampus of sevoflurane anesthetized aged mice. Methods Sixty Kunming aged mice were randomly divided into control group(n=20), model group(n=20) and test group(n=20). Model group and test group were inhaled 3% sevoflurane for 4 h, and control group was inhaled 100% oxygen for 4 h. The mice in test group were intraperitoneally injected with dexmedetomidine hydrochloride 10 μL before inhaling 3% sevoflurane;control and model groups were intraperitoneally injected with 0. 9% NaCl 10 μL. The cognitive function of the mice was measured by Morris water maze tester and open field experiment. Immunohistochemistry and Western blotting( Wb) method were used to detect the expression of p Creb and Egr1 proteins in hippocampus. Results The escape latencies of mice in control,model and test groups on the 4 thd were( 17. 28 ± 3. 24),( 27. 73 ± 5. 92) and( 22. 96 ± 3. 75) s;the times of crossing the original platform were( 5. 64 ± 1. 21),( 2. 97 ± 0. 72) and( 4. 83 ± 1. 16) times;the number of crossings the grid were( 90. 21 ± 18. 02),( 41. 52 ± 9. 03),( 73. 64 ± 17. 11) times;the number of standing on the back legs were( 11. 63 ± 3. 37),( 4. 23 ± 1. 12),( 8. 56 ± 1. 54) times;the time spent in the central square were( 9. 37 ± 1. 69),( 32. 83 ± 7. 65),( 14. 24 ± 2. 51) s. On the 1 stto 4 thd of the positioning experiment,the escape latency of 3 groups of mice were gradually shortened,but model group and test group were significantly longer than control group,and test group was shorter than model group,with significant difference( P < 0. 05). Compared with control group,the times of crossing the original platform,the number of crossing the grid and the number of standing on the back legs in model group were significantly reduced, and test group was more than model group, with significant difference( all P < 0. 05). The time spent in the central square was longer,and test group was shorter than model group,with significant difference( P < 0. 05);the percentage of pCreb and Egr1 protein-positive cells and relative expression in hippocampus of model group were significantly lower than that of control group,while test group was higher than model group,with significant difference( P < 0. 05). Conclusion Dexmedetomidine can improve cognitive function in aged mice after sevoflurane anesthesia,and its mechanism may be related to up-regulation of pCreb and Egr1 protein expression in hippocampus.