Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CC...Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay.The protein expressions of SIRT1 and p38 MAPK were measured by Western blot.RT-qPCR was also used to determine SIRT1 mRNA expression.In addition,intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated.Results:Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability.It also increased SIRT1 and decreased p-p38 MAPK protein expressions.In addition,thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress,and enhanced antioxidant enzyme activities.However,silencing SIRT1 abrogated the protective effects of thrombopoietin,as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels.Conclusions:Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway.However,its protective effects need to be further verified in animal tests.展开更多
目的观察阿伐曲泊帕联合重组人血小板生成素(rhTPO)对恶性血液病自体造血干细胞移植(ASCT)后血小板(PLT)植入的临床疗效。方法回顾性分析76例ASCT患者的临床资料,其中40例阿伐曲泊帕(avatrombopag,AVA)联合rhTPO升血小板治疗为观察组,36...目的观察阿伐曲泊帕联合重组人血小板生成素(rhTPO)对恶性血液病自体造血干细胞移植(ASCT)后血小板(PLT)植入的临床疗效。方法回顾性分析76例ASCT患者的临床资料,其中40例阿伐曲泊帕(avatrombopag,AVA)联合rhTPO升血小板治疗为观察组,36例rhTPO单药治疗为对照组。比较两组患者PLT水平、PLT植入时间、PLT输注数量、PLT谷值及Ⅳ级血小板减少持续时间,记录不良反应。结果观察组PLT植入时间短于对照组[(11.15±1.08)d v s.(12.61±2.65)d,(P<0.05)],且PLT输注单位数少于对照组[2(1.00,2.75)U v s.3(2.00,4.00)U,(P<0.001)];阿伐曲泊帕联合rhTPO促血小板治疗的第5天、第10天、第15天,血小板计数均高于相应单药对照组,药物干预后的第5天及第10天血小板植入率有所提高(P<0.05)。多元线性回归分析显示,阿伐曲泊帕是影响PLT植入时间的独立因素(P<0.001),其使用可将植入时间缩短1.598天。两组患者均观察到出血事件,以皮肤黏膜出血点、瘀斑、牙龈出血为主,出血发生率无差异。两组均无血栓形成及凝血障碍发生。结论阿伐曲泊帕联合rhTPO能有效升高ASCT患者PLT计数,促进PLT植入,二者联用有协同作用,且耐受良好。展开更多
基金supported by the Natural Science Foundation of Hainan Province High-level Talent Project(grant number 820RC644)Innovative Research Projects for Postgraduate Students at Hainan Medical University(grant number HYYS2022B08).
文摘Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay.The protein expressions of SIRT1 and p38 MAPK were measured by Western blot.RT-qPCR was also used to determine SIRT1 mRNA expression.In addition,intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated.Results:Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability.It also increased SIRT1 and decreased p-p38 MAPK protein expressions.In addition,thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress,and enhanced antioxidant enzyme activities.However,silencing SIRT1 abrogated the protective effects of thrombopoietin,as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels.Conclusions:Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway.However,its protective effects need to be further verified in animal tests.
文摘目的观察阿伐曲泊帕联合重组人血小板生成素(rhTPO)对恶性血液病自体造血干细胞移植(ASCT)后血小板(PLT)植入的临床疗效。方法回顾性分析76例ASCT患者的临床资料,其中40例阿伐曲泊帕(avatrombopag,AVA)联合rhTPO升血小板治疗为观察组,36例rhTPO单药治疗为对照组。比较两组患者PLT水平、PLT植入时间、PLT输注数量、PLT谷值及Ⅳ级血小板减少持续时间,记录不良反应。结果观察组PLT植入时间短于对照组[(11.15±1.08)d v s.(12.61±2.65)d,(P<0.05)],且PLT输注单位数少于对照组[2(1.00,2.75)U v s.3(2.00,4.00)U,(P<0.001)];阿伐曲泊帕联合rhTPO促血小板治疗的第5天、第10天、第15天,血小板计数均高于相应单药对照组,药物干预后的第5天及第10天血小板植入率有所提高(P<0.05)。多元线性回归分析显示,阿伐曲泊帕是影响PLT植入时间的独立因素(P<0.001),其使用可将植入时间缩短1.598天。两组患者均观察到出血事件,以皮肤黏膜出血点、瘀斑、牙龈出血为主,出血发生率无差异。两组均无血栓形成及凝血障碍发生。结论阿伐曲泊帕联合rhTPO能有效升高ASCT患者PLT计数,促进PLT植入,二者联用有协同作用,且耐受良好。
