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)/含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。
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.
作者
张洪江
李树霞
翁洪亮
ZHANG Hongjiang;LI Shuxia;WENG Hongliang(Department of Anesthesiology,Linyi Central Hospital,Linyi 276400,China;不详)
出处
《实用医学杂志》
CAS
北大核心
2022年第7期848-852,共5页
The Journal of Practical Medicine
基金
临沂市科技创新发展计划项目(编号:202020033)。