Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues...Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.展开更多
目的探究下肢动脉硬化闭塞症(ASO)患者血清miR-150和miR-155水平表达对支架植入术再狭窄(ISR)的预测价值。方法选取2020年3月~2022年6月期间在德阳市人民医院接受支架植入治疗的108例ASO患者,根据其术后一年是否发生ISR,分为发生ISR组(n...目的探究下肢动脉硬化闭塞症(ASO)患者血清miR-150和miR-155水平表达对支架植入术再狭窄(ISR)的预测价值。方法选取2020年3月~2022年6月期间在德阳市人民医院接受支架植入治疗的108例ASO患者,根据其术后一年是否发生ISR,分为发生ISR组(n=42)和未发生ISR组(n=66)。实时荧光定量聚合酶链式反应(qRT-PCR)检测患者血清中miR-150和miR-155的相对表达水平;采用Pearson相关性分析血清miR-150,miR-155水平与低密度脂蛋白-胆固醇(LDL-C)、超敏C反应蛋白(hs-CRP)的相关性;采用多因素Logistic回归分析影响ASO患者发生ISR的因素;采用受试者工作特征(ROC)曲线分析血清miR-150,miR-155水平对ASO患者发生ISR的预测价值。结果与未发生ISR组相比,发生ISR组血清miR-150(0.65±0.16 vs 1.01±0.09)水平显著降低,miR-155(1.68±0.39 vs 1.02±0.11),LDL-C(2.85±0.76 mmol/L vs 2.21±0.62mmol/L),hs-CRP(2.36±0.47 mg/L vs 1.82±0.36mg/L)水平显著升高,差异具有统计学意义(t=4.785~14.957,均P<0.05)。经Pearson相关性分析显示,血清miR-150与LDL-C,hs-CRP水平呈显著负相关(r=-0.465,-0.532,均P<0.05),血清miR-155与LDL-C,hs-CRP水平呈显著正相关(r=0.453,0.481,均P<0.05)。多因素Logistic回归分析显示,血清miR-150是影响ASO患者发生ISR的保护因素,血清miR-155,LDL-C和hs-CRP为影响ASO患者发生ISR的危险因素(均P<0.05)。ROC曲线分析显示,血清miR-150,miR-155及二者联合预测ASO患者发生ISR的AUC(95%CI)分别为0.869(0.791~0.926),0.874(0.796~0.930)及0.976(0.926~0.996),联合检测显著优于二者单独预测(Z=2.679,2.745,均P<0.05)。结论ASO支架植入术后发生ISR的患者血清miR-150水平降低,miR-155水平升高,均是影响ASO患者发生ISR的因素,且二者联合具有较高的预测价值。展开更多
基金supported by the Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9233(to HH)the QuanzhouScience and Technology Project,No.2022C036R(to HH)+1 种基金the Science and Technology Bureau of Quanzhou,No.2020CT003(to SL)the Quanzhou MunicipalMedical and Health Guiding Science and Technology Project,No.2023N066S(to YZhou).
文摘Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.
文摘目的探究下肢动脉硬化闭塞症(ASO)患者血清miR-150和miR-155水平表达对支架植入术再狭窄(ISR)的预测价值。方法选取2020年3月~2022年6月期间在德阳市人民医院接受支架植入治疗的108例ASO患者,根据其术后一年是否发生ISR,分为发生ISR组(n=42)和未发生ISR组(n=66)。实时荧光定量聚合酶链式反应(qRT-PCR)检测患者血清中miR-150和miR-155的相对表达水平;采用Pearson相关性分析血清miR-150,miR-155水平与低密度脂蛋白-胆固醇(LDL-C)、超敏C反应蛋白(hs-CRP)的相关性;采用多因素Logistic回归分析影响ASO患者发生ISR的因素;采用受试者工作特征(ROC)曲线分析血清miR-150,miR-155水平对ASO患者发生ISR的预测价值。结果与未发生ISR组相比,发生ISR组血清miR-150(0.65±0.16 vs 1.01±0.09)水平显著降低,miR-155(1.68±0.39 vs 1.02±0.11),LDL-C(2.85±0.76 mmol/L vs 2.21±0.62mmol/L),hs-CRP(2.36±0.47 mg/L vs 1.82±0.36mg/L)水平显著升高,差异具有统计学意义(t=4.785~14.957,均P<0.05)。经Pearson相关性分析显示,血清miR-150与LDL-C,hs-CRP水平呈显著负相关(r=-0.465,-0.532,均P<0.05),血清miR-155与LDL-C,hs-CRP水平呈显著正相关(r=0.453,0.481,均P<0.05)。多因素Logistic回归分析显示,血清miR-150是影响ASO患者发生ISR的保护因素,血清miR-155,LDL-C和hs-CRP为影响ASO患者发生ISR的危险因素(均P<0.05)。ROC曲线分析显示,血清miR-150,miR-155及二者联合预测ASO患者发生ISR的AUC(95%CI)分别为0.869(0.791~0.926),0.874(0.796~0.930)及0.976(0.926~0.996),联合检测显著优于二者单独预测(Z=2.679,2.745,均P<0.05)。结论ASO支架植入术后发生ISR的患者血清miR-150水平降低,miR-155水平升高,均是影响ASO患者发生ISR的因素,且二者联合具有较高的预测价值。
