CAJ | 학술논문

目的探讨氯胺酮麻醉对7d龄SD大鼠成年后情绪的影响及其机制.方法选取7d龄(P7)SD大鼠40只,随机分为两组:分别腹腔注射生理盐水0.25 ml(NS组)和氯胺酮组50 mg/kg(K组),每隔30 min重复1次,共4次.6h后各组随机取5只幼鼠前额皮质,行Western blot检测半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3的表达水平;余饲养至30 d行行为学测试:糖水偏好实验(SPT)及旷场实验(0FT);随后取脑行尼氏染色检测前额皮质神经元密度.结果麻醉后6h,K组幼鼠前额皮质Caspase-3的表达显著升高,差异有统计学意义(n=5,P＜0.05);30 d时,K组大鼠前额皮质第Ⅲ层神经元密度明显低于NS组[NS组:(1 367±79)/mm2,K组:(1 105±73)/mm2,n=6,P ＜0.05];30d时,和NS组比较,K组SD大鼠中心区探索时间显著减少[NS组:(25.9±2.2)s,K组:(16.5±2.0)s,n=15,P＜0.01];且糖水饮用率显著降低[NS组:(77.0±2.5)％,K组:(60.0±4.3)％,n=15,P＜0.01].结论 SD大鼠幼年期氯胺酮麻醉后可致成年抑郁和焦虑样情绪障碍,可能和前额皮质区凋亡相关蛋白表达增加及神经元密度下降有关.
목적 탐토록알동마취대7d령SD대서성년후정서적영향급기궤제.방법 선취7d령(P7)SD대서40지,수궤분위량조:분별복강주사생리염수0.25 ml(NS조)화록알동조50 mg/kg(K조),매격30 min중복1차,공4차.6h후각조수궤취5지유서전액피질,행Western blot검측반광안선천동안산특이성단백매(Caspase)-3적표체수평;여사양지30 d행행위학측시:당수편호실험(SPT)급광장실험(0FT);수후취뇌행니씨염색검측전액피질신경원밀도.결과 마취후6h,K조유서전액피질Caspase-3적표체현저승고,차이유통계학의의(n=5,P＜0.05);30 d시,K조대서전액피질제Ⅲ층신경원밀도명현저우NS조[NS조:(1 367±79)/mm2,K조:(1 105±73)/mm2,n=6,P ＜0.05];30d시,화NS조비교,K조SD대서중심구탐색시간현저감소[NS조:(25.9±2.2)s,K조:(16.5±2.0)s,n=15,P＜0.01];차당수음용솔현저강저[NS조:(77.0±2.5)％,K조:(60.0±4.3)％,n=15,P＜0.01].결론 SD대서유년기록알동마취후가치성년억욱화초필양정서장애,가능화전액피질구조망상관단백표체증가급신경원밀도하강유관.
Objective To investigate the effect of ketamine administration to neonatal SD rats on prefrontal cortex development and emotional state in adult.Methods Forty postnatal day 7 (P7) SD rats were randomly assigned to receive intraperitoneal injection of 50 mg/kg ketamine (K group) or 0.25 ml saline (NS group),once every 30 min for totally 4 times.The expression of cysteinyl aspartate-specific protease-3 (Caspase-3) in the prefrontal cortex was detected by Western blotting at 6 h after the last injection,and the remaining pups were allowed to grow up with their mothers until P30.Behavioral tests were done to evaluate cognitive function and mood state on P30-P33.After behavioral tests,rats were sacrificed for Nissl staining to study the cytoarchitecture development of prefrontal cortex.Results P7 rats exposed to ket-amine caused up-regulated expression of Caspase-3 in the prefrontal cortex (n =5,P ＜ 0.05).At P30,as compared with control group,the center area of the environment [NS group:(25.9 ± 2.2) s,K group:(16.5±2.0) s,n=15,P＜0.01],sucrose intake [NS group:(77.0±2.5)％,K group:(60.0±4.3) ％,n =15,P ＜ 0.01],and the cell density in the prefrontal cortex [NS group:(1 367 ± 79) cells/mm2,K group:(1 105 ± 73) cells/mm2,n =6,P ＜ 0.05] were significandy reuced in K group.Conclusion Administration of ketamine to neonatal SD rats causes depression-and anxiety-like behaviors in adult,which may be associated with cell apoptosis by up-regulating the Caspase-3 expresion and neuronal loss in the prefrontal cortex.