实用临床医药杂志2024，Vol.28Issue(19)：41-47,54,8.DOI:10.7619/jcmp.20243234
微小RNA-34a调控CaMK Ⅱ/CREB途径改善异氟烷麻醉引起的老年大鼠认知功能障碍
MicroRNA-34a regulates the CaMK Ⅱ/CREB pathway to improve isoflurane anesthesia-induced cognitive dysfunction in aged rats
摘要
Abstract
Objective To investigate the effects and underlying mechanisms of microRNA(miR)-34a on isoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods Forty rats at 20 months of age were randomly divided into control(Con)group,model group,miR-34a inhibitor group and miR-34a mimics group,with 10 rats in each group.Rats in the miR-34a inhibitor and miR-34a mimics groups received a tail vein injection of 100 nmoL/kg of the corresponding drug,while those in the Con and model groups received an equal volume of saline,once daily for 5 consecu-tive days.At the 6th day,all groups except the Con group underwent a single 6-hour isoflurane anes-thesia to establish a postoperative cognitive dysfunction(POCD)model.Twelve hours after modeling,the Morris water maze test was used to assess the escape latency and time spent in the target quadrant.Immunofluorescence staining was performed to observe the positive expression rate of ionized calci-um-binding adapter molecule 1(Iba-1)in the hippocampal tissue.Real-time quantitative polymer-ase chain reaction(qRT-PCR)was used to measure the relative expression levels of miR-34a,B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X-protein(Bax)mRNA in the hippocampal tissue.Enzyme-linked immunosorbent assay(ELISA)was conducted to detect serum levels of interleukin-6(IL-6),interleukin-1 β(IL-1β),reactive oxygen species(ROS)and glutathione peroxidase(GSH-Px),as well as the content of glutamate(Glu),Ca2+and N-methyl-D-aspartate receptor 2B(NMDAR2B)in the hippocampal tissue.Western blotting was used to determine the relative ex-pression levels of calcium-calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ),phosphorylated CaMK Ⅱ(pCaMK Ⅱ),cyclophosphoadenosine effector-binding protein(CREB),and phosphoryla-ted CREB(pCREB)in the hippocampal tissue.Results Compared with the Con group,the Model group exhibited significantly prolonged escape latency,elevated serum levels of IL-6 and IL-1β and ROS,as well as increased positive expression rate of Iba-1,relative expression levels of miR-34a and Bax mRNA,contents of Glu,Ca2+and NMDAR2B in the hippocampal tissue;in contrast,the time spent in the target quadrant,serum GSH-Px levels,Bcl-2 mRNA relative expression levels,Bcl-2/Bax,as well as pCaMK Ⅱ/CaMK Ⅱ and pCREB/CREB in the hippocampal tissue were sig-nificantly reduced(P＜0.05).Downregulation of miR-34a expression shortened the escape latency and decreased serum levels of IL-6,IL-1 β and ROS,as well as Iba-1 positive expression rate,rela-tive expression levels of miR-34a and Bax mRNA,Glu,Ca2+and NMDAR2B content in the hipp-ocampal tissue(P＜0.05).It also extended the time spent in the target quadrant and increased ser-um GSH-Px levels,Bcl-2 mRNA expression levels,Bcl-2/Bax,as well as pCaMK Ⅱ/CaMK Ⅱ and pCREB/CREB in the hippocampal tissue(P＜0.05).Upregulation of miR-34a expression promo-ted abnormal activation of microglia,inflammation,oxidative stress and apoptosis,inhibited the ac-tivation of the CaMK Ⅱ/CREB signaling pathway,and exacerbated cognitive dysfunction in the mod-el rats.Conclusion MiR-34a is highly expressed in POCD in aged rats.Inhibition of miR-34a ex-pression can improve isoflurane anesthesia-induced cognitive dysfunction in aged rats by activating the CaMK Ⅱ/CREB signaling pathway.关键词
微小RNA-34a/异氟烷/认知功能障碍/炎症/钙-钙调蛋白依赖性蛋白激酶Ⅱ/环磷腺苷效应元件结合蛋白Key words
microRNA-34a/isoflurane/cognitive function disorder/inflammation/calcium-calmodulin-dependent protein kinase Ⅱ/cyclophosphoadenosine effector binding protein分类
医药卫生引用本文复制引用
唐林,刘慧敏,罗柳,付卫东..微小RNA-34a调控CaMK Ⅱ/CREB途径改善异氟烷麻醉引起的老年大鼠认知功能障碍[J].实用临床医药杂志,2024,28(19):41-47,54,8.基金项目
湖南省创新型省份建设专项项目(S2021JJZZLH0913) （S2021JJZZLH0913）
