Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effect...Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.Methods:Male Sprague-Dawley rats(n=130)were randomly divided into blank control(Con),sham operation(Sham),AF,and acupuncture treatment(Acu)groups.A paroxysmal AF model was established by rapid atrial pacing through the jugular vein.Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint(PC6)for 20 min daily for seven days.The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture.The AF induction rate,AF duration,cardiac electrophysiological parameters,and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals.After the intervention,the rats were euthanized,and atrial morphology was assessed using haematoxylin and eosin staining.The expression of macrophage F4/80 antigen(F4/80)and cluster of differentiation(CD)86 in atrial myocardial tissue was detected using immunohistochemistry,immunofluorescence and flow cytometry.The expression levels or contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-a(TNF-a),a7 nicotinic acetylcholine receptor(a7nAChR),phosphorylated Janus kinase 2(p-JAK2),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)in atrial myocardial tissue were detected using Western blotting,reverse transcription-quantitative polymerase chain reaction,or enzyme-linked immunosorbent assay.The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine(MLA).Results:Compared with the AF group,acupuncture significantly reduced AF duration and induction rate,improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance.It also decreased the pro-inflammatory M1 macrophage proportion,alleviating myocardial injury and infiltration.MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect.Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.Conclusion:Acupuncture significantly reduced the AF induction rate,shortened AF duration,improved cardiac electrophysiological parameters,enhanced vagus nerve activity,and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF.展开更多
目的探究S100钙结合蛋白A7(S100 cabinding protein A7,S100A7)、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)在Ⅰ型子宫内膜癌(endometrial...目的探究S100钙结合蛋白A7(S100 cabinding protein A7,S100A7)、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)在Ⅰ型子宫内膜癌(endometrial carcinoma,EC)组织中的表达及临床意义。方法选取60例Ⅰ型EC患者组织和30例正常子宫内膜组织,运用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RT-qPCR)方法,检测各组织中S100A7、IGF-1、RAGE mRNA的表达情况。采用免疫组化法检测107例Ⅰ型EC组织、24例非典型增生内膜组织和30例正常内膜组织中S100A7、IGF-1、RAGE的蛋白表达情况,分析三者的相关性以及与患者临床病理特征的关系,采用Kaplan-Meier法绘制生存曲线,COX回归分析影响患者生存预后的因素。结果与正常内膜组织比较,S100A7、IGF-1、RAGE mRNA在EC组织中的表达升高(P<0.05)。S100A7、IGF-1、RAGE蛋白阳性率随着内膜病变的进展而升高,且三者呈正相关(P<0.05)。不同国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)分期、有无淋巴结转移、不同组织分化程度Ⅰ型EC组织S100A7、IGF-1、RAGE的阳性率不同(P<0.05)。Kaplan-Meier生存分析结果显示,S100A7、IGF-1、RAGE阳性表达患者的平均生存时间短于阴性表达患者。COX回归分析结果显示,淋巴结转移、高表达S100A7、高表达IGF-1及高表达RAGE是Ⅰ型子宫内膜癌患者预后的独立危险因素。结论S100A7、IGF-1、RAGE在Ⅰ型EC组织中的表达水平增高,三者的阳性表达与子宫内膜癌的发生、发展和不良预后密切有关。展开更多
应用咪喹莫特(imiquimod,IMQ)诱导的银屑病小鼠模型以及五联因子(a mixture of five proinflammatory cytokines,M5)诱导的银屑病角质形成细胞模型,评价羧胺三唑(carboxyamidotriazole,CAI)对银屑病的治疗效果和可能机制。银屑病皮损面...应用咪喹莫特(imiquimod,IMQ)诱导的银屑病小鼠模型以及五联因子(a mixture of five proinflammatory cytokines,M5)诱导的银屑病角质形成细胞模型,评价羧胺三唑(carboxyamidotriazole,CAI)对银屑病的治疗效果和可能机制。银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分评估小鼠皮损严重程度,苏木素-伊红(hematoxylin-eosinstaining,HE)染色观察皮肤病理学变化,酶联免疫吸附法(enzyme-linked immunosorbentassay,ELISA)检测皮肤中细胞因子水平,转录组测序分析差异表达基因,实时荧光定量PCR(real-time quantitative PCR,qPCR)检测mRNA表达。动物实验经中国医学科学院基础医学研究所实验动物管理与伦理委员批准(批准号:ACUC-A02-2022-115)。结果显示,与IMQ组相比,CAI显著改善小鼠银屑病样皮损,降低PASI评分,减轻皮损病理变化和评分,减少皮损处促炎细胞因子水平,转录组分析结果显示CAI可能通过调节角质形成细胞及其介导的表皮角化而发挥作用,qPCR验证发现CAI能够下调差异表达基因S100a7;进一步使用M5刺激HaCaT细胞构建银屑病角质形成细胞模型,CAI能够抑制M5诱导的S100a7以及细胞因子的mRNA水平。综上,CAI可能对银屑病具有良好治疗作用,其作用机制与调节角质形成细胞功能以及减少细胞因子和S100a7表达有关。展开更多
基金supported by the National Key Research and Development Program of China(No.2019YFC1712100)the National Natural Science Foundation of China(No.82105017)。
文摘Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.Methods:Male Sprague-Dawley rats(n=130)were randomly divided into blank control(Con),sham operation(Sham),AF,and acupuncture treatment(Acu)groups.A paroxysmal AF model was established by rapid atrial pacing through the jugular vein.Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint(PC6)for 20 min daily for seven days.The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture.The AF induction rate,AF duration,cardiac electrophysiological parameters,and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals.After the intervention,the rats were euthanized,and atrial morphology was assessed using haematoxylin and eosin staining.The expression of macrophage F4/80 antigen(F4/80)and cluster of differentiation(CD)86 in atrial myocardial tissue was detected using immunohistochemistry,immunofluorescence and flow cytometry.The expression levels or contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-a(TNF-a),a7 nicotinic acetylcholine receptor(a7nAChR),phosphorylated Janus kinase 2(p-JAK2),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)in atrial myocardial tissue were detected using Western blotting,reverse transcription-quantitative polymerase chain reaction,or enzyme-linked immunosorbent assay.The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine(MLA).Results:Compared with the AF group,acupuncture significantly reduced AF duration and induction rate,improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance.It also decreased the pro-inflammatory M1 macrophage proportion,alleviating myocardial injury and infiltration.MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect.Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.Conclusion:Acupuncture significantly reduced the AF induction rate,shortened AF duration,improved cardiac electrophysiological parameters,enhanced vagus nerve activity,and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF.
文摘目的探究S100钙结合蛋白A7(S100 cabinding protein A7,S100A7)、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)在Ⅰ型子宫内膜癌(endometrial carcinoma,EC)组织中的表达及临床意义。方法选取60例Ⅰ型EC患者组织和30例正常子宫内膜组织,运用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RT-qPCR)方法,检测各组织中S100A7、IGF-1、RAGE mRNA的表达情况。采用免疫组化法检测107例Ⅰ型EC组织、24例非典型增生内膜组织和30例正常内膜组织中S100A7、IGF-1、RAGE的蛋白表达情况,分析三者的相关性以及与患者临床病理特征的关系,采用Kaplan-Meier法绘制生存曲线,COX回归分析影响患者生存预后的因素。结果与正常内膜组织比较,S100A7、IGF-1、RAGE mRNA在EC组织中的表达升高(P<0.05)。S100A7、IGF-1、RAGE蛋白阳性率随着内膜病变的进展而升高,且三者呈正相关(P<0.05)。不同国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)分期、有无淋巴结转移、不同组织分化程度Ⅰ型EC组织S100A7、IGF-1、RAGE的阳性率不同(P<0.05)。Kaplan-Meier生存分析结果显示,S100A7、IGF-1、RAGE阳性表达患者的平均生存时间短于阴性表达患者。COX回归分析结果显示,淋巴结转移、高表达S100A7、高表达IGF-1及高表达RAGE是Ⅰ型子宫内膜癌患者预后的独立危险因素。结论S100A7、IGF-1、RAGE在Ⅰ型EC组织中的表达水平增高,三者的阳性表达与子宫内膜癌的发生、发展和不良预后密切有关。
文摘应用咪喹莫特(imiquimod,IMQ)诱导的银屑病小鼠模型以及五联因子(a mixture of five proinflammatory cytokines,M5)诱导的银屑病角质形成细胞模型,评价羧胺三唑(carboxyamidotriazole,CAI)对银屑病的治疗效果和可能机制。银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分评估小鼠皮损严重程度,苏木素-伊红(hematoxylin-eosinstaining,HE)染色观察皮肤病理学变化,酶联免疫吸附法(enzyme-linked immunosorbentassay,ELISA)检测皮肤中细胞因子水平,转录组测序分析差异表达基因,实时荧光定量PCR(real-time quantitative PCR,qPCR)检测mRNA表达。动物实验经中国医学科学院基础医学研究所实验动物管理与伦理委员批准(批准号:ACUC-A02-2022-115)。结果显示,与IMQ组相比,CAI显著改善小鼠银屑病样皮损,降低PASI评分,减轻皮损病理变化和评分,减少皮损处促炎细胞因子水平,转录组分析结果显示CAI可能通过调节角质形成细胞及其介导的表皮角化而发挥作用,qPCR验证发现CAI能够下调差异表达基因S100a7;进一步使用M5刺激HaCaT细胞构建银屑病角质形成细胞模型,CAI能够抑制M5诱导的S100a7以及细胞因子的mRNA水平。综上,CAI可能对银屑病具有良好治疗作用,其作用机制与调节角质形成细胞功能以及减少细胞因子和S100a7表达有关。
