中国病理生理杂志2026，Vol.42Issue(4)：686-695,10.DOI:10.3969/j.issn.1000-4718.2026.04.007
miR-483-5p通过调控小胶质细胞M1/M2极化减轻心肺复苏后大鼠神经功能损伤
miR-483-5p regulates microglial M1/M2 polarization to attenuate neuro-logical injury after cardiopulmonary resuscitation
摘要
Abstract
AIM:To elucidate the role and underlying molecular mechanism of microRNA-483-5p(miR-483-5p)in regulating microglial polarization and neurological outcomes following cardiopulmonary resuscitation(CPR).METHODS:In vivo,an asphyxia-induced cardiac arrest(CA)/CPR model was established in Wistar rats.Four weeks before CA/CPR induction,an empty adeno-associated virus serotype 9(AAV9)vector(AAV9-NC),an AAV9 vector ex-pressing a negative control sponge(AAV9-sponge-NC),an AAV9 vector expressing miR-483-5p(AAV9-miR-483-5p),and an AAV9 vector expressing a miR-483-5p sponge(AAV9-sponge-miR-483-5p)were stereotactically injected into the lateral ventricle.Sixty rats were randomly assigned to 6 groups:sham,CA/CPR,CA/CPR+AAV9-NC,CA/CPR+AAV9-sponge-NC,CA/CPR+AAV9-miR-483-5p,and CA/CPR+AAV9-sponge-miR-483-5p groups(n=10).Hippocampal histo-pathology was assessed using HE and Nissl staining.Neurological function was evaluated by neurological deficit score and Morris water maze test.Microglial activation was determined by immunofluorescence staining for ionized calcium-binding adapter molecule 1(Iba1)in the hippocampus.Protein expression levels of microglial polarization markers and inflamma-tory mediators were quantified by Western blot analysis.In vitro,an oxygen-glucose deprivation/reoxygenation(OGD/R)model was established in BV2 microglial cells.The cells were randomly divided into the following groups:NC,OGD/R,OGD/R+LV-NC,OGD/R+miR-483-5p mimic,and OGD/R+miR-483-5p inhibitor.The miR-483-5p expression was quan-tified using RT-qPCR.Western blot,immunofluorescence staining and flow cytometry were used to assess the protein ex-pression levels and positive rates of microglial polarization-related markers.RESULTS:Following CA/CPR,miR-483-5p expression was significantly down-regulated in the hippocampus,concomitant with enhanced microglial activation and a shift towards the pro-inflammatory(M1)phenotype,along with impaired neurological function.Overexpression of miR-483-5p markedly reduced hippocampal histopathological damage,improved neurological performance,and promoted mi-croglial polarization toward the anti-inflammatory M2 phenotype,thereby enhancing neurological outcomes.Consistently,in vitro experiments further demonstrated that OGD/R promoted M1 polarization of BV2 microglia and increased pro-inflam-matory cytokine expression.Overexpression of miR-483-5p facilitated M2 polarization,whereas its inhibition promoted M1 polarization and exacerbated inflammatory responses.CONCLUSION:miR-483-5p may attenuate post-resuscitation brain injury and improve neurological outcomes by regulating microglial polarization from the pro-inflammatory M1 pheno-type toward the anti-inflammatory M2 phenotype.关键词
复苏后脑损伤/微小RNA-483-5p/小胶质细胞极化/神经炎症Key words
post-resuscitation brain injury/microRNA-483-5p/microglial polarization/neuroinflammation分类
医药卫生引用本文复制引用
刘可可,张强,黎博,黄文峰,胡春林,卢远征..miR-483-5p通过调控小胶质细胞M1/M2极化减轻心肺复苏后大鼠神经功能损伤[J].中国病理生理杂志,2026,42(4):686-695,10.基金项目
四大慢病重大专项(No.2023ZD0505500) （No.2023ZD0505500）
广东省基础与应用基础研究基金(No.2024A1515010799 （）
No.2023A1515011792) （）
中山大学附属第七医院(深圳)急救复苏研究所"415计划"项目(No.ZSQY202441501) （深圳）
