上海交通大学学报(医学版)

• 论著(基础研究) • 上一篇    下一篇

右美托咪定对术后老龄小鼠海马组织白介素1β和肿瘤坏死因子α表达的影响

钱晓岚1,2,3,王庆端2,张 卫4,周玉冰4,江金花2,张晶敏2   

  1. 1.郑州大学 药学院, 郑州 450001; 2.郑州大学医药科学研究所, 郑州 450052; 3.河南省直第三人民医院麻醉科, 郑州 450006; 4.郑州大学第一附属医院麻醉科; 郑州 450052
  • 出版日期:2015-02-28 发布日期:2015-02-27
  • 通讯作者: 王庆端, 电子信箱: Wangqd@zzu.edu.cn。
  • 作者简介:钱晓岚(1969—), 女, 副主任医师, 博士生; 电子信箱: qianxiaolan05@126.com。
  • 基金资助:

    河南省医学科技攻关计划项目(201304073)

Effects of dexmedetomidine on expressions of IL-1β and TNF-α in hippocampus tissues of aged mice after surgery

QIAN Xiao-lan1,2.3, WANG Qing-duan2, ZHANG Wei4, ZHOU Yu-bing4, JIANG Jin-hua2, ZHANG Jing-min2   

  1. 1.School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; 2.Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China; 3.Department of Anesthesiology, the Third People's Hospital of Henan Province, Zhengzhou 450006, China; 4.Department of Anesthesiology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
  • Online:2015-02-28 Published:2015-02-27
  • Supported by:

    Medical Science and Technology Tackling Plan of Henan Province, 201304073

摘要:

目的 探讨右美托咪定对手术创伤后老龄小鼠海马组织白介素1β (IL-1β)和肿瘤坏死因子α (TNF-α)表达以及术后认知功能障碍(POCD)的影响。方法 将105只老龄昆明小鼠随机分为4组。空白对照组(n=15):不实施麻醉和手术;麻醉药物组(n=30):腹腔注射氯胺酮100 mg/kg,持续吸入异氟醚60 min;麻醉药物+手术组(n=30):给予复合麻醉药物后实施剖腹探查脾切除手术;右美托咪定干预组(n=30):术前30 min各取15只小鼠分别给予右美托咪定15、25 μg/kg腹腔内注射。术后第1日、第3日行Y迷宫实验(右美托咪定干预组在术后第3日进行),记录各组所需的训练次数;荧光定量PCR 和Western blotting检测海马组织IL-1β、TNF-α mRNA及蛋白的表达。结果 与空白对照组比较,麻醉药物组术后第1日训练次数增多(P<0.05),术后第3日恢复正常(P>0.05),麻醉药物+手术组术后第1日、第3日训练次数增多(P<0.01,P<0.05);术后第3日,右美托咪定15、25 μg/kg干预组与空白对照组比较,差异均无统计学意义(P>0.05)。与空白对照组比较,麻醉药物+手术组术后第1日、第3日IL-1β、TNF-α mRNA及蛋白的表达量均显著升高(P<0.05或P<0.01);麻醉药物组术后第1日、第3日及右美托咪定干预组术后第3日IL-1β、TNF-α mRNA及蛋白的表达量与空白对照组比较,差异无统计学意义(P>0.05)。结论 右美托咪定预处理能降低小鼠海马组织IL-1β、TNF-α mRNA及蛋白的表达,其改善小鼠POCD的作用与抑制海马炎症反应有关。

关键词: 右美托咪定, 炎症, 白介素1β, 肿瘤坏死因子α, 手术, 术后认知功能障碍, 老龄小鼠

Abstract:

Objective To explore the effects of dexmedetomidine on expressions of IL-1 β and TNF-α in hippocampus tissues of aged mice after surgery and postoperative cognitive decline (POCD). Methods A total of 105 aged Kunming mice were randomly divided into 4 groups, i.e. control group (n=15) that received no anesthesia and surgery, anesthesia group (n=30) that received consecutive isoflurane inhalation for 60 min and intraperitoneal injection of ketamine of 100 mg/kg, splenectomized group (n=30) that underwent splenectomy after anesthesia, intervention group (n=30) that received intraperitoneal injection of dexmedetomidine of 15 and 25 μg/kg (15 mice for each dose) 30 min before anesthesia and surgery. Y-maze experiments were conducted 1 d and 3 d after surgery (Y-maze experiments were conducted 3 d after surgery for the intervention group). The trial numbers of each group were recorded. The mRNA and protein expressions of IL-1β and TNF-α in hippocampus tissues were detected by the qRT-PCR and Western blotting. Results The trial number of the anesthesia group was more than that of the control group 1 d after surgery (P<0.05) and was back to normal 3 d after surgery (P>0.05). The trial number of the splenectomized group was more than that of the control group 1 d and 3 d after surgery (P<0.01, P<0.05). The differences of the intervention group and control group 3 d after surgery were not statistically significant (P>0.05). Compared with the control group, the mRNA and protein expressions of IL-1β and TNF-α of the splenectomized group significantly increased 1 d and 3 d after surgery (P<0.05 or P<0.01), and the differences of the mRNA and protein expressions of IL-1β and TNF-α of the anesthesia group (1 d and 3 d after surgery), intervention group (3 d after surgery), and control group were not statistically significant (P>0.05). Conclusion Pretreatment with dexmedetomidine can decrease the mRNA and protein expressions of IL-1β and TNF-α in hippocampus tissues of mice. The improvement of POCD of mice is relevant to the inhibition of inflammation responses of hippocampus.

Key words: dexmedetomidine, inflammation, interleukin-1β, tumor necrosis factor-α, surgery, postoperative cognitive dysfunction, aged mice