氯胺酮麻醉对乳鼠脑细胞凋亡的影响

Effect of Ketamine on Triggering Neuronal Apoptosis in the Neonatal Rat Brain

目的探讨临床上常用的麻醉剂氯胺酮对乳鼠脑细胞凋亡的影响。方法新生7日龄SD大鼠15只,随机分成3组:氯胺酮低剂量组、高剂量组分别腹腔注射20 mg/kg、80 mg/kg氯胺酮,对照组给予等量的生理盐水。麻醉后24 h,取脑组织作HE染色,用TUNEL法检测脑细胞的凋亡情况,用免疫组织化学法检测Caspase-3的表达水平。结果与对照组比较,氯胺酮低剂量组的凋亡细胞增多但不明显(P>0.05),神经元核固缩和Caspase-3阳性细胞数明显增多(P<0.05);氯胺酮高剂量组的凋亡细胞数、神经元核固缩及Caspase-3阳性细胞数显著性增加(P<0.05)。神经元核固缩、凋亡细胞和Caspase-3阳性细胞均以皮层区多见。结论 80 mg/kg氯胺酮可引起乳鼠脑细胞凋亡,以皮层区为主,Caspase-3的激活可能是其作用机制之一;20 mg/kg氯胺酮对乳鼠脑细胞凋亡的影响较轻微,其临床等效剂量为3 mg/kg。氯胺酮小儿麻醉用量不宜过多,避免引起脑细胞的凋亡。

Objective To investigate the effect of ketamine on neuronal apoptosis in the neonatal rat brain.Methods Fifteen 7-day-old Sprague-Dawley rats were randomly divided into 3 groups（n = 5 each）,and received intraperitoneal（i.p） injection with saline（control）,keamine 20 mg /kg and ketamine 80 mg /kg respectively.Apoptotic neurons were observed by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling（TUNEL） and the Caspase-3 expression was detected by immunohistochemical method.Results Compared with the control group,the TUNEL positive cells were increased but no obvious difference（P 0.05）,the Karyopyknosis neuron number and the Caspase-3 positive cells were significantly increased in 20 mg /kg ketamine group（P 0.05）,the TUNEL positive cells,the Karyopyknosis neuron number and the Caspase-3 positive cells were significantly increased in 80 mg /kg ketamine group（P 0.05）.The apoptotic cells,the Karyopyknosis neuron number and the Caspase positive cells in ketamine group were mostly seen in cortical area.Conclusions 80 mg /kg ketamine can induce neuronal apoptosis in the neonatal rat brain,the cortical area is the main target organ,Caspase-3 activation may be one of the mechanisms.The effect of 20 mg /kg Ketamineon triggering neuronal apoptosis in the neonatal rat brain is minor,the clinical equivalent dose of 20 mg /kg ketamine is 3 mg /kg.The amount of ketamine anesthesia in children should not be too many for avoiding causing brain cells apoptosis.