国际麻醉学与复苏杂志   2015, Issue (9): 2-2
    
右美托咪定减轻七氟醚诱导的新生大鼠海马细胞凋亡和远期认知障碍
吴新海, 邓若熹, 张燕1()
1.北京大学深圳医院麻醉科
Dexmedetomidine alleviate the apoptosis of hippocampus cell and long-term cognitive dysfunction induced by sevoflurane in neonatal rats
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摘要：

目的　探讨腹腔注射右美托咪定（dexmedetomidine， Dex）能否减轻七氟醚诱导的新生大鼠海马细胞凋亡和远期认知功能障碍。　方法　48只出生7 d的Sprague-Dawley（SD）大鼠采用随机数字表法分为4组（每组12只）：对照组（C组）、25 μg/kg Dex单纯腹腔注射组（D组）、3%七氟醚吸入组（S组）和25 μg/kg Dex干预组（DS组），每组实验连续重复3 d。吸入处理后每组又采用随机数字表法分为2个亚组（A组和B组，每组6只），A组2 h后用Western blot法检测组织内海马激活型Caspase-3，脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（terminal-deoxynucleotidyl transferase mediated nick end labeling， TUNEL）检测海马CA1区细胞凋亡；B组继续饲养到3周后采用Morris水迷宫实验评估大鼠的学习和记忆功能。　结果　S组和DS组新生大鼠CA1区TUNEL阳性细胞［（45±5）， （33±6） 个/mm2］高于C组［（18±4） 个/mm2］（P<0.05）；S组和DS组新生大鼠CA1区激活型Caspase-3表达［（1.40±0.25），（1.22±0.15）］高于对照组（0.30±0.20）（P<0.05）；与S组比较，DS组新生大鼠的CA1区TUNEL阳性细胞和激活型Caspase-3表达减少（P<0.05）。与C组比较，S组和DS组新生大鼠远期的认知和学习能力下降；与S组比较，DS组新生大鼠远期的认知和学习能力增强。　结论　多次吸入3％的七氟醚能诱导新生大鼠海马细胞凋亡和认知功能障碍，而预先腹腔注射25 μg/kg Dex能减轻七氟醚诱导的海马细胞凋亡和远期认识功能障碍。
关键词： 右美托咪定；　七氟醚；　认知功能障碍；　海马；　凋亡
Abstract:

Ｏｂｊｅｃｔｉｖｅ　To investigate whether dexmedetomidine（Dex） could alleviate the apoptosis of hippocampus cell and long-time cognitive dysfunction induced by sevoflurane（Sev） in neonatal rats.　Methods　Forty-eight Sprague-Dawley（SD） rats in postnatal 7 d were randomly assigned into 4 groups（n=12）： control group（group C）， 25 μg/kg Dex intraperitoneal injection group（group D）， 3% Sev inhaling group（group S） and 25 μg/kg Dex intervention group（group DS）. Each group was randomly divided into 2 subgroups（subgroup A and subgroup B， 6 rats in every subgroup）. Twenty-four hours after completion of Sev exposure in subgroup A， the activation of caspase-3 in hippocampus were analyzed by Western blot， and the neuronal apoptosis in the CA1 region of the hippocampus were detected by terminal-deoxynucleotidyl transferase mediated nick end labeling（TUNEL） method. The rats' cognitive function was evaluated using Morris maze experiment in subgroup B.　Results　Compared with group C， the expression of TUNEL positive cells in group S and group DS increased［（45±5）/mm2 vs （18±4）/mm2 and （33±6）/mm2 vs （18±4）/mm2， respectively］（P<0.05）. Compared with group C， the expression of cleaved Caspase-3 in group S and group DS increased［（1.40±0.25） vs （0.30±0.20） and （1.22±0.15） vs（0.30±0.20）， respectively］（P<0.05）. The expression of TUNEL positive cells and cleaved Caspase-3 decreased in group DS compared with group S（P<0.05）. Compared with group C. The cognitive function of rats declined in the group S and group DS. Compared with group S， the cognitive dysfunction of rats alleviated in group DS.　Conclusions　Repeatedly inhaling 3% Sev can induce the apoptosis of hippocampus cells and long-time cognitive dysfunction. 25 μg/kg Dex intraperitoneal injection before inhaling Sev can alleviate the neurotoxicity induced by Sev.
Key words: Dexmedetomidine；　Sevoflurane；　Cognitive dysfunction；　Hippocampus；　Apoptosis