氯胺酮诱导发育期大鼠神经细胞凋亡时神经甾体17β雌二醇水平的变化  

Changes in Level of 17β-estradiol when Ketamine Induces Neuroapoptosis in the Developing Rat Brain

作　　者：李建立[1] 崔红赏[2] 郭洪霞[1] 于洋[3] 吴红海[3] 侯艳宁[3] 

机构地区：[1]河北省人民医院麻醉科,石家庄050051 [2]河北省人民医院胸外科,石家庄050051 [3]白求恩国际和平医院药剂科,石家庄050082

出　　处：《福建医科大学学报》2016年第2期93-97,共5页Journal of Fujian Medical University

基　　金：河北省卫生厅医学重点课题(ZL20140095)

摘　　要：目的探讨连续大剂量应用氯胺酮引起发育期大鼠大脑皮层区神经细胞凋亡时神经甾体17β雌二醇水平的变化及机制。方法 30只7日龄雄性SD大鼠,随机分为对照组和氯胺酮组,每组15只。对照组连续3d腹腔注射等容量生理盐水,氯胺酮组连续3d腹腔注射75mg/kg氯胺酮,末次注药后24h,每组取5只大鼠用免疫组织化学法检测大脑皮层区cleaved-caspase-3和CYP19A1的表达,其余幼鼠应用高效液相色谱-质谱联用法(HPLC-MS/MS)测定大脑皮层区神经甾体17β雌二醇的含量。结果与对照组比较,氯胺酮组大鼠大脑皮层区cleaved-caspase-3阳性细胞显著性增加(P<0.01),17β雌二醇水平及CYP19A1酶的表达均显著性下降(P<0.01)。结论连续大剂量应用氯胺酮可引起发育期大鼠大脑皮层区神经细胞凋亡伴随神经甾体17β雌二醇水平下降,其机制可能与限速酶CYP19A1表达下降有关。Objective To investigate the effect of ketamine on 17β-estradiol level in the developing rat brain. Methods 30 aged 7days SD male rats were randomly divided into two group：Group C and Group K. Group C was intraperitoneally injected with same volume of saline for three consecutive days,Group K was intraperitoneally injected with 75mg/kg ketamine for three consecutive days.24 hours after the last injection,five rats from each group were decapitated under deep anesthesia and the PFC portion was isolated to detect cleaved caspase-3and CYP19A1 expressions by immunohistochemical analysis（n=5）. The PFC of other rats was harvested to determine 17β-estradiol concentration by HPLC-MS/MS assay（n=10）. Results Compared with the Group C,the expression of cleaved caspase-3in Group K increased significantly after being treated with 75 mg/kg ketamine for three consecutive days（P〈0.01）,while 17β-estradiol level and CYP19A1 expression in PFC significantly reduced（P〈0.01）. ConclusionKetamine can cause decrease in the endogenous 17β-estradiol level,which was associated with the decrease of CYP19A1 expression.

关 键 词：氯胺酮 雌二醇 细胞凋亡 色谱法 高压液相 质谱分析法 基因 

分 类 号：R965[医药卫生—药理学]