磷酸二酯酶4B与小鼠阿霉素心脏毒性相关性研究  

Correlation between phosphodiesterase 4B and doxorubicin-induced cardiotoxicity in mice

作　　者：布雨鑫 王静 王雅妮 武翰林 邹宇佳 刘美丽 刘丹 BU Yu-xin;WANG Jing;WANG Ya-ni;WU Han-lin;ZOU Yu-jia;LIU Mei-li;LIU Dan(Department of Cardiovascology,National Key Laboratory of Cold Geocentric Vascular Disease,General Hospital of Northern Theater Command,Shenyang 110016,China)

机构地区：[1]北部战区总医院、寒地心血管病全国重点实验室、心血管内科,辽宁沈阳110016

出　　处：《临床军医杂志》2024年第6期602-604,608,共4页Clinical Journal of Medical Officers

基　　金：国家自然科学基金面上项目(82070308);辽宁省优秀青年基金计划项目(2021-YQ-03);辽宁省科技计划联合基金面上项目(2023-MSLH-366)。

摘　　要：目的探讨磷酸二酯酶4B(PDE4B)与小鼠阿霉素心脏毒性(DIC)的相关性。方法将12只C57BL/6J小鼠随机分入生理盐水组和DIC组,每组各6只。DIC组采用腹腔注射阿霉素(DOX)建立小鼠DIC模型。注射DOX后第15天,超声评价生理盐水组和DIC组小鼠的心功能。采用实时荧光定量聚合酶链式反应和Western blot检测生理盐水组、DIC组PDE4B mRNA及PDE4B蛋白水平。采用DOX刺激HL-1心肌细胞24 h后,实时荧光定量聚合酶链式反应和Western Blot检测对照组(未给予DOX刺激)、DOX组(给予DOX刺激)PDE4B mRNA及PDE4B蛋白水平。结果与生理盐水组比较,DIC组小鼠的左室射血分数和短轴缩短率均显著降低(P<0.05)。与生理盐水组比较,DIC组心肌组织PDE4B mRNA及蛋白水平均明显升高(P<0.05)。在心肌细胞中,与对照组比较,DOX组PDE4B mRNA及蛋白水平均明显升高(P<0.05)。结论PDE4B在DOX刺激后心肌组织和心肌细胞中表达升高。Objective To investigate the correlation between phosphodiesterase 4B(PDE4B)and doxorubicin-induced cardiotoxicity(DIC)in mice.Methods Twelve C57BL/6J mice were randomly divided into saline group and DIC group,with 6 mice in each group.In the DIC group,doxorubicin(DOX)was injected intraperitoneally to establish a mouse DIC model.On day 15 after DOX injection,the cardiac function of mice in saline group and DIC group was evaluated by ultrasound.Real-time quantitative reverse transcription polymerase chain reaction(PCR)and Western blot were used to detect PDE4B mRNA and PDE4B protein levels in saline group and DIC group.After DOX stimulation of HL-1 cardiomyocytes for 24 h,real-time quantitative reverse transcription PCR and Western Blot were used to detect PDE4B mRNA and PDE4B protein levels in control group(not given DOX stimulation)and DOX group(given DOX stimulation).Results Compared with saline group,left ventricular ejection fraction and short axis shortening rate in DIC group were significantly decreased(P<0.05).Compared with saline group,the mRNA and protein levels of PDE4B in myocardial tissue of DIC group were significantly increased(P<0.05).In cardiomyocytes,compared with control group,the mRNA and protein levels of PDE4B of DOX group were significantly increased(P<0.05).Conclusion The expression of PDE4B is increased in myocardial tissue and cardiomyocytes after DOX stimulation.

关 键 词：磷酸二酯酶4B 阿霉素 阿霉素心脏毒性 心肌组织 

分 类 号：R542.22[医药卫生—心血管疾病]