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
Objective:To investigate the role of T helper 9(Th9) cells in liver cirrhosis(LC) patients and whether chemokine receptor type 6(CCR6)/chemokine ligand 20(CCL20) axis is involving in the recruitment of Th9 cells into ...Objective:To investigate the role of T helper 9(Th9) cells in liver cirrhosis(LC) patients and whether chemokine receptor type 6(CCR6)/chemokine ligand 20(CCL20) axis is involving in the recruitment of Th9 cells into liver.Methods:Peripheral blood and liver tissue from 30 LC patients and 18 normal controls were recruited.The frequency of Th9 cells and CCR4,CCR6 in the peripheral blood was tested by flow cytometry.Serum interleukin(IL)-9 and CCL20 levels were tested by enzyme-linked immunosorbent assay.Immunohistochemical staining was used to detect a-smooth muscle actin,CCR6 and CCL20 expression in liver tissue.Results:The frequency of Th9 cells in LC patients was significantly increased compared with controls(P < 0.05).The serum IL-9 level and CCL20 level increased markedly in LC patients compared with controls(P < 0.05),and IL-9 was positively correlated to Th9 cells and CCL20.Furthermore,the frequency of Th9 cells was correlated to prothrombin time,total bilirubin level,hyaluronic acid and type IV collagen in LC patients.We also found that Th9 cells in LC patients expressed higher frequency of CCR4+,CCR6+(P < 0.05).Compared with normal controls,the expression of CCR6 and CCL20 in LC tissue were significantly elevated(P < 0.05).The expression of a-smooth muscle actin was correlated to the CCR6 and CCL20 in liver tissue of LC patients.Conclusions:This study suggests that Th9 cells may participate in the pathogenesis of LC,and the recruitment of Th9 cells into liver tissue might be through CCL20/CCR6 axis.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.
基金Supported by grants from the National Natural Science Foundation of China(81260083,31360221)Natural Science Foundation of Guangxi Province(2014GXNSFAA118203)
文摘Objective:To investigate the role of T helper 9(Th9) cells in liver cirrhosis(LC) patients and whether chemokine receptor type 6(CCR6)/chemokine ligand 20(CCL20) axis is involving in the recruitment of Th9 cells into liver.Methods:Peripheral blood and liver tissue from 30 LC patients and 18 normal controls were recruited.The frequency of Th9 cells and CCR4,CCR6 in the peripheral blood was tested by flow cytometry.Serum interleukin(IL)-9 and CCL20 levels were tested by enzyme-linked immunosorbent assay.Immunohistochemical staining was used to detect a-smooth muscle actin,CCR6 and CCL20 expression in liver tissue.Results:The frequency of Th9 cells in LC patients was significantly increased compared with controls(P < 0.05).The serum IL-9 level and CCL20 level increased markedly in LC patients compared with controls(P < 0.05),and IL-9 was positively correlated to Th9 cells and CCL20.Furthermore,the frequency of Th9 cells was correlated to prothrombin time,total bilirubin level,hyaluronic acid and type IV collagen in LC patients.We also found that Th9 cells in LC patients expressed higher frequency of CCR4+,CCR6+(P < 0.05).Compared with normal controls,the expression of CCR6 and CCL20 in LC tissue were significantly elevated(P < 0.05).The expression of a-smooth muscle actin was correlated to the CCR6 and CCL20 in liver tissue of LC patients.Conclusions:This study suggests that Th9 cells may participate in the pathogenesis of LC,and the recruitment of Th9 cells into liver tissue might be through CCL20/CCR6 axis.
