郑仲磊,范晓英,杜克信
ZHEN Zhonglei,FAN Xiaoying,DU Kexin

• 1:西安医学院第二附属医院手麻科

摘要(Abstract)：

目的:探讨七氟烷与丙泊酚对老年大鼠认知功能的影响及机制。方法:30只SD雄性老年(18～20月龄)大鼠,均分为对照组(正常通气)、七氟烷组(吸入3%七氟烷)和丙泊酚组(腹腔注射50 mg/kg丙泊酚);造模第7～14天时,采用Morris水迷宫实验记录逃避潜伏期和穿越平台次数;造模第14天时,取3组大鼠海马组织,采用HE染色及透射电镜观察病理损伤情况,酶联免疫吸附(ELISA)法检测肿瘤坏死因子-α(TNF)及白细胞介素-6 (IL-6)含量,TUNEL法检测细胞凋亡情况,免疫荧光和Western blot检测Caspase-3、Bax、Bcl-2、p-NF-κB和IκB等蛋白的表达水平。结果:Morris水迷宫结果显示,3组大鼠逃避潜伏期丙泊酚组>七氟烷组>对照组,3组大鼠穿过平台次数丙泊酚组<七氟烷组<对照组(P <0. 05); HE染色结果显示,对照组大鼠海马CA1区锥体细胞排列整齐致密,细胞形态正常、核仁及细胞质清晰,七氟烷组神经元明显减少、锥体神经元排列松散、不规则,丙泊酚组形态学改变相对七氟烷组轻;透射电镜结果显示,对照组大鼠海马神经元细胞核结构完整,排列规则;七氟烷组海马元神经的细胞核发生明显变化,细胞核膜开始内陷,结构不完整,丙泊酚组细胞核轻度内陷,呈半月板状; 3组大鼠海马组织TNF-α及IL-6含量,凋亡指数,Bax、p-NF-κB、Caspase-3、Bax及p-NF-κB蛋白表达水平比较,七氟烷组>丙泊酚组>对照组(P <0. 05); Bcl-2和IκB蛋白表达水平比较,七氟烷组<丙泊酚组<对照组(P <0. 05)。结论:七氟烷和丙泊酚均对老年大鼠认知功能产生影响,其机制可能与NF-κB和Bax/Caspase-3信号通路有关,丙泊酚的影响轻于七氟烷。
Objective: To investigate the effects of sevoflurane and propofol on cognitive function of aged rats and its mechanism. Methods: Thirty SD male aged rats were selected as experimental animals. Each group with10 rats was randomly divided into the control group,the sevoflurane group and the propofol group,of which the sevoflurane group was inhaled and given 3% sevoflurane and the propofol group. Intraperitoneal injection of 50 mg/kg propofol,Morris water maze test was used to evaluate the cognitive function of the rats from the 7 th and 14 th days after the modeling. On the 14 th day,brain tissue was removed,and HE staining and transmission electron microscopy were used. Elisa method was used to observe the pathological damage of rat hippocampus and detect the content of TNF-α and IL-6 in rat brain tissues; TUNEL method to observe the apoptosis of brain tissue cells and immunofluorescence and Western blot to detect Caspase-3 in brain tissues,Bax,Bcl-2,p-NF-κB and IκB protein expression levels. Results: Compared with the control group, the latency of the sevoflurane group and the propofol group significantly increased,and the frequency of crossing the platform was significantly reduced. The levels of TNF-α and IL-6 in the brain tissues significantly increased,and CA1 in the hippocampus significantly increased. The neurons in the area were significantly reduced,the pyramidal neurons were arranged loosely and irregularly,some neurons showed nuclear shrinkage and excessive cytoplasm,the nuclear membrane of hippocampal nerve cells invaded,and immunohistochemical and Western blot results showed that the expressions of Caspase-3,Bax and p-NF-κB protein in the sevoflurane group and propofol group were significantly higher than those in the control group,and Bcl-2 and IκB significantly decreased. In the comparison between the sevoflurane group and the propofol group,the indexes of propofol were significantly lower in the propofol group than those of the sevoflurane group. Conclusion: Sevoflurane and propofol can obviously induce apoptosis and inflammatory response in the hippocampus of aged rats,causing cognitive dysfunction. The mechanism may be related to NF-κB and Bax/Caspase-3 signaling pathways. The effect of propofol on cognitive function is lower than that of sevoflurane.

关键词(KeyWords)： 大鼠,Sprague-Dawley;免疫组织化学;七氟烷;丙泊酚;老年;认知功能障碍
rats,sprague-dawley;immunohistochemistry;sevoflurane;propofol;aged;cognitive function

Abstract:

Keywords:

基金项目(Foundation): 陕西省科学技术厅社会发展攻关项目(2016SF-166)

作者(Author): 郑仲磊,范晓英,杜克信
ZHEN Zhonglei,FAN Xiaoying,DU Kexin

DOI: 10.19367/j.cnki.2096-8388.2020.05.011

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