实用医学杂志 ›› 2022, Vol. 38 ›› Issue (7): 848-852.doi: 10.3969/j.issn.1006⁃5725.2022.07.013

• 基础研究 • 上一篇    下一篇

miR⁃223调控NLRP3/Caspase⁃1通路在氯胺酮诱导发育期大鼠海马神经元焦亡中的作用

张洪江1 李树霞2 翁洪亮1   

  1. 临沂市中心医院1 麻醉科,2 病理科(山东临沂 276400)

  • 出版日期:2022-04-10 发布日期:2022-04-10
  • 通讯作者: 翁洪亮 E⁃mail:ysmzwhl@126.com
  • 基金资助:
    临沂市科技创新发展计划项目(编号:202020033)

The role of miR⁃223 in ketamine⁃induced pyrolysis of hippocampal neurons in rats by regulating the NL⁃ RP3/Caspase ⁃ 1 pathway

ZHANG Hongjiang*,LI Shuxia,WENG Hongliang.   

  1. Department of Anesthesiology Linyi Central HospitalLinyi 276400China 

  • Online:2022-04-10 Published:2022-04-10
  • Contact: WENG Hongliang E⁃mail:ysmzwhl@126.com

摘要:

目的 探究微小 RNA 223(miR⁃223)调控 NOD 样受体热蛋白结构域相关蛋白 3(NLRP3)/ 半胱氨酸的天冬氨酸蛋白水解酶 1(Caspase⁃1)通路在氯胺酮诱导发育期大鼠海马神经元焦亡中的作用。 方法 50 只大鼠分为对照组、氯胺酮组、agomir⁃NC 组、agomir⁃223 组、agomir⁃223+BAY11⁃7082 组,每组 10 只;qRT⁃PCR 检测大鼠海马组织中 miR⁃223 表达水平,空间探索实验检测 miR⁃223 对大鼠认知功能的影 响,HE 染色与TUNEL 染色检测大鼠海马组织病理学改变。分析miR⁃223过表达对大鼠海马神经元凋亡以 及白介素 18(Interleukin 18,IL⁃18)、白介素 1β(Interleukin 1β,IL⁃1β)的影响,Western blot 检测各组大鼠海 马组织中 NLRP3、cleaved Caspase⁃1、GSDMD⁃N 的表达情况。结果 与对照组相比,氯胺酮组大鼠潜伏 期、海马组织病理学程度、神经元凋亡、白介素 18(IL⁃18)、白介素 1β(IL⁃1β)、NLRP3、cleaved Caspase⁃1 GSDMD⁃N水平增加,穿越平台次数、第三象限停留时间占比、miR⁃223水平降低(P < 0.05);与氯胺酮组相比, agomir⁃223 组潜伏期、海马组织病理学程度、神经元凋亡、IL⁃18、IL⁃1β、NLRP3、cleaved Caspase⁃1、GSDMD⁃N 水平降低,穿越平台次数、第三象限停留时间占比、miR⁃223 水平增加(P < 0.05)。结论 miR⁃223 过表达 可能通过抑制NLRP3/Caspase⁃1通路来改善氯胺酮诱导发育期大鼠海马神经元焦亡。

关键词:

微小RNA 223, 氯胺酮, 神经元, 焦亡, 含半胱氨酸的天冬氨酸蛋白水解酶1

Abstract:

Objective To explore the role of microRNA⁃223(miR⁃223)in ketamine⁃induced pyrolysis of hippocampal neurons in rats at a developmental phase by regulating the Nod⁃like receptor pyrin domain⁃containing protein 3(NLRP3)/cysteinyl aspartate specific proteinase 1(Caspase⁃1)pathway. Methods Rats were divided into a control group,ketamine group,agomir⁃NC group,agomir⁃223 group,agomir⁃223+BAY11⁃7082 group,10 for each group. Western blot was used to detect expressions of NLRP3,cleaved Caspase⁃1 and GSDMD⁃N in the rat hippocampus. Results As compared with the control group,the incubation period,hippocampal histopathology neuronal apoptosis,levels of interleukin⁃18(IL⁃18),interleukin⁃1β(IL⁃1β),NLRP3,cleaved Caspase⁃1,and GSDMD⁃N increased in the ketamine group;while the number of crossing platforms,the proportion of time staying in the third quadrant,and the level of miR⁃223 reduced(P < 0.05). As compared with the ketamine group,the incubation period,hippocampal histopathology,neuronal apoptosis,levels of IL ⁃18,IL ⁃1β,NLRP3,cleaved Caspase⁃1,and GSDMD⁃N reduced in the agomir⁃223 group,whereas the number of crossing platforms,the proportion of time staying in the third quadrant,and the level of miR ⁃ 223 increased(P < 0.05). Conclusions Overexpression of miR⁃223 may improve ketamine⁃induced hippocampal neuronal pyrolysis in rats at a developmental phase by inhibiting the NLRP3/Caspase⁃1 pathway.

Key words:

microRNA 223, ketamine, neuron, pyrolysis, cysteinyl aspartate specific proteinase 1