目的探讨C-C趋化因子受体9(CCR9)/C-C基序趋化因子配体25(CCL25)轴对阿霉素(DOX)诱导的心脏毒性的影响.方法将60只野生型C57BL/6J小鼠随机分为四组:对照组(CTL组,n=15)、腹腔注射阿霉素组(DOX组,n=15)、腹腔注射阿霉素+尾静脉注射生理...目的探讨C-C趋化因子受体9(CCR9)/C-C基序趋化因子配体25(CCL25)轴对阿霉素(DOX)诱导的心脏毒性的影响.方法将60只野生型C57BL/6J小鼠随机分为四组:对照组(CTL组,n=15)、腹腔注射阿霉素组(DOX组,n=15)、腹腔注射阿霉素+尾静脉注射生理盐水组(DOX+NS组,n=15)、腹腔注射阿霉素+尾静脉注射抗CCL25中和抗体组(DOX+anti-CCL25组,n=15);造模7天后,超声心动图评估小鼠心功能;使用程序化电刺激记录小鼠在体心脏的单向动作电位时程(MAPD)、有效不应期(ERP)、电交替(ALT)阈值和室性心律失常的诱发率.结果与CTL组相比,DOX组左室射血分数(LVEF)和短轴缩短分数(FS)显著降低,左心室舒张末期内径(LVIDd)和左心室收缩末期内径(LVIDs)显著增加(P均<0.05);30%单向动作电位时程(MAPD30)、MAPD50、MAPD70、MAPD90和动作电位复极化时限三角测量值(triangulation)均延长,ERP延长,ALT阈值降低(P均<0.05);10 V和20 V Burst刺激下室性心律失常的诱发率和S1S1程序化刺激下室性心律失常的诱发率均显著升高(P均<0.008);与DOX组相比,DOX+anti-CCL25组LVEF和FS显著升高,LVIDd和LVIDs减小(P均<0.05);MAPD70、MAPD90、Triangulation和ERP缩短(P均<0.05).结论DOX导致小鼠心脏结构重构和电重构,发生室性心律失常的易感性增加,抗CCL25中和抗体可以明显改善DOX小鼠心脏的结构重构和电重构,CCR9/CCL25通路在阿霉素诱导的心脏毒性中有重要作用.展开更多
慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD,慢阻肺)是一种由气道炎症和气道重塑(airway remodeling, AR)引起的一种常见的慢性呼吸系统疾病。其中,气道重塑与COPD的进展之间存在的正反馈环显示了气道重塑在COPD进...慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD,慢阻肺)是一种由气道炎症和气道重塑(airway remodeling, AR)引起的一种常见的慢性呼吸系统疾病。其中,气道重塑与COPD的进展之间存在的正反馈环显示了气道重塑在COPD进展中的重要性。目前气道重塑的具体机制不明。临床上通过胸部CT发现的气道异常常提示患者已经发生了气道重塑,因此,寻找识别早期气道重塑的方法至关重要。研究表明,基质金属蛋白酶-9 (matrix metalloproteinase-9, MMP-9)、金属蛋白酶组织抑制剂-1 (tissue inhibitor of metalloproteinase-1, TIMP-1)、及MMP-9/TIMP-1比值之间的失衡参与COPD的气道重塑过程,本文叙述了MMP-9、TIMP-1及MMP-9/TIMP-1比值作为非侵入性诊断标志物在COPD气道重塑方面的研究进展,期待能提高人们对早期气道重塑的认知,希望能为将来气道重塑靶向药的问世尽一份绵薄之力。Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease caused by airway inflammation and airway remodeling (AR). Among them, the positive feedback loop between airway remodeling and the progression of COPD shows the importance of airway remodeling in the progress of COPD. At present, the specific mechanism of airway remodeling is unknown. Airway abnormalities found by chest CT often indicate that airway remodeling has occurred in patients. Therefore, it is very important to find a method to identify early airway remodeling. Studies have shown that the imbalance between matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and MMP-9/TIMP-1 ratio is involved in the airway remodeling of COPD. This paper describes the research progress of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio as non-invasive diagnostic markers in airway remodeling of COPD. It is expected to improve people’s understanding of early airway remodeling and make a modest contribution to the development of targeted drugs for airway remodeling in the future.展开更多
文摘目的探讨C-C趋化因子受体9(CCR9)/C-C基序趋化因子配体25(CCL25)轴对阿霉素(DOX)诱导的心脏毒性的影响.方法将60只野生型C57BL/6J小鼠随机分为四组:对照组(CTL组,n=15)、腹腔注射阿霉素组(DOX组,n=15)、腹腔注射阿霉素+尾静脉注射生理盐水组(DOX+NS组,n=15)、腹腔注射阿霉素+尾静脉注射抗CCL25中和抗体组(DOX+anti-CCL25组,n=15);造模7天后,超声心动图评估小鼠心功能;使用程序化电刺激记录小鼠在体心脏的单向动作电位时程(MAPD)、有效不应期(ERP)、电交替(ALT)阈值和室性心律失常的诱发率.结果与CTL组相比,DOX组左室射血分数(LVEF)和短轴缩短分数(FS)显著降低,左心室舒张末期内径(LVIDd)和左心室收缩末期内径(LVIDs)显著增加(P均<0.05);30%单向动作电位时程(MAPD30)、MAPD50、MAPD70、MAPD90和动作电位复极化时限三角测量值(triangulation)均延长,ERP延长,ALT阈值降低(P均<0.05);10 V和20 V Burst刺激下室性心律失常的诱发率和S1S1程序化刺激下室性心律失常的诱发率均显著升高(P均<0.008);与DOX组相比,DOX+anti-CCL25组LVEF和FS显著升高,LVIDd和LVIDs减小(P均<0.05);MAPD70、MAPD90、Triangulation和ERP缩短(P均<0.05).结论DOX导致小鼠心脏结构重构和电重构,发生室性心律失常的易感性增加,抗CCL25中和抗体可以明显改善DOX小鼠心脏的结构重构和电重构,CCR9/CCL25通路在阿霉素诱导的心脏毒性中有重要作用.
文摘慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD,慢阻肺)是一种由气道炎症和气道重塑(airway remodeling, AR)引起的一种常见的慢性呼吸系统疾病。其中,气道重塑与COPD的进展之间存在的正反馈环显示了气道重塑在COPD进展中的重要性。目前气道重塑的具体机制不明。临床上通过胸部CT发现的气道异常常提示患者已经发生了气道重塑,因此,寻找识别早期气道重塑的方法至关重要。研究表明,基质金属蛋白酶-9 (matrix metalloproteinase-9, MMP-9)、金属蛋白酶组织抑制剂-1 (tissue inhibitor of metalloproteinase-1, TIMP-1)、及MMP-9/TIMP-1比值之间的失衡参与COPD的气道重塑过程,本文叙述了MMP-9、TIMP-1及MMP-9/TIMP-1比值作为非侵入性诊断标志物在COPD气道重塑方面的研究进展,期待能提高人们对早期气道重塑的认知,希望能为将来气道重塑靶向药的问世尽一份绵薄之力。Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease caused by airway inflammation and airway remodeling (AR). Among them, the positive feedback loop between airway remodeling and the progression of COPD shows the importance of airway remodeling in the progress of COPD. At present, the specific mechanism of airway remodeling is unknown. Airway abnormalities found by chest CT often indicate that airway remodeling has occurred in patients. Therefore, it is very important to find a method to identify early airway remodeling. Studies have shown that the imbalance between matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and MMP-9/TIMP-1 ratio is involved in the airway remodeling of COPD. This paper describes the research progress of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio as non-invasive diagnostic markers in airway remodeling of COPD. It is expected to improve people’s understanding of early airway remodeling and make a modest contribution to the development of targeted drugs for airway remodeling in the future.
