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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

26卷

期数:

2020年05期

页码:

418-421

栏目:

基础医学

出版日期:

2020-09-20

文章信息/Info

Title:

Dexmedetomidine ameliorates sevoflurane-induced neurotoxicity in neonatal mice via the pathway of α7nAChR-HDAC6

文章编号:

1006-8147(2020)05-0418-04

作者:

朱敏; 于洪丽; 孙英; 杜洪印; 喻文立

（南开大学附属天津市第一中心医院麻醉科，天津 300192）

Author(s):

ZHU Min;  YU Hong-li;  SUN Ying;  DU Hong-yin; YU Wen-li

（Department of Anesthesiology, Tianjin First Central Hospital Affiliated to Nankai University, Tianjin，300192, China）

关键词:

右美托咪啶; 七氟烷; α7烟碱型乙酰胆碱受体; 组蛋白去乙酰化酶6

Keywords:

dexmedetomidine; sevoflurane; α7nicotinic acetylcholine receptor; histone deacetylase 6

分类号:

R614

DOI:

-

文献标志码:

A

摘要:

目的：探讨α7烟碱型乙酰胆碱受体(α7nAChR)-组蛋白去乙酰化酶6(Histone deacetylase 6, HDAC6)通路在右美托咪啶降低幼鼠七氟烷神经毒性的作用。方法：7 d龄Sprague-Dawley(SD)大鼠 随机分为5组（n =40）：空白对照组（C组），七氟烷麻醉组（S组），右美托咪啶对照组（D组），七氟烷+右美托咪啶组（SD组），七氟烷+右美托咪啶+抑制剂MLA组（M组）。将幼鼠置于3%七氟烷培养 箱2 h，连续3 d构建七氟烷模型。ELISA法检测幼鼠脑组织促炎因子（TNF-α、IL1β和IL-6）和脑损伤标志物（S-100β和NSE）；尼式染色检测海马神经元CA1区存活情况；Western 印迹检测海马 α7nAChR和HDAC6蛋白表达；Y迷宫实验检测幼鼠认知水平。结果：S组幼鼠TNF-α、IL1β、IL-6和S-100β、NSE表达增加，α7nAChR降低，HDAC6增加，海马CA1区神经元存活降低，认知功能下降；右美 托咪啶预处理降低七氟烷毒性；MLA可逆转右美托咪啶保护作用。结论：右美托咪啶降低七氟烷麻醉幼鼠神经毒性，其机制与α7nAChR- HDAC6通路有关。

Abstract:

Objective: To investigate the effect of dexmedetomidine on sevoflurane- induced neurotoxicity in neonatal mice via the pathway of α7nAChR- HDAC6. Methods：Postnatal day 7 Sprague-Dawley (male) rats were randomly divided into 5 groups (n=40): blank control group(Group C), sevoflurane anesthesia group(Group S), right metoclopramide control group(Group D), sevoflurane and right metoclopramide group (Group SD), sevoflurane and right metoclopramide with inhibitor MLA group (group M). Neonatal mice were exposed to 3% sevoflurane 2 hours for 3 days with or without 25 μg/kg dexmedetomidine intraperitoneal injection. The inflammatory cytokines (TNF-α, IL-6, IL-18 and IL-10) and brain injury factors(S-100β and NSE) were determined by ELISA. Nissl staining was performed to survey the number of survival neurons in hippocampal CA1 area. The expression of α7nAChR and HDAC6 protein was analyzed by Western blot. The cognitive behavioral data of rats were collected at P41(the beginning of the adult stage) using Y-maze experiment. Results：There were statistically increased of TNF-α, IL1β, IL-6, S-100β, NSE, and HDAC6 protein expression, decreased of the number of suriving neurons in hippocampal CA1 area, expression of α7nAChR and cognitive function in group S(P<0.05). Dexmedetomidine provided the neuroprotectives from sevoflurane injury. Moreover, the inhibitor MLA significantly eliminated the protective effect of dexmedetomidine on sevoflurane injury. Conclusion：Dexmedetomidine provide neuroprotection in a rat model of sevoflurane-induced neurotoxicity, which is related to α7nAChR-HDAC6 signaling pathway.

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备注/Memo

备注/Memo:

基金项目 天津市自然科学基金面上项目（18JCYBJC27500、17JCYBJC28000）；天津市临床重点学科（麻醉学科）建设项目；天津市卫生计生委科技攻关项目（16KG101）；天津市麻醉学会恩华基金项目（2017）
作者简介 朱敏（1987-），男，住院医师，硕士，研究方向：脑保护；
通信作者：喻文立，E-mail：yzxyuwenli@163.com。

常用功能

更新日期/Last Update: 2020-09-18