地奥心血康对阿霉素诱导的斑马鱼心脏毒性保护作用的研究  

Protective effect of Di'ao Xinxuekang on doxorubicin-induced cardiotoxicity in zebrafish

作　　者：邓良艳 刘佳[1] 瞿礼萍[1] 邹文俊[1] DENG Liangyan;LIU Jia;QU Liping;ZOU Wenjun(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Sichuan Chengdu 61l137,China)

机构地区：[1]成都中医药大学药学院,四川成都611137

出　　处：《中药与临床》2025年第2期28-33,共6页Pharmacy and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(82274324);四川省自然科学基金杰出青年科学基金(24NSFJQ0125)。

摘　　要：目的:观察地奥心血康(DXXK)对阿霉素(doxorubicin,DOX)诱导的斑马鱼心脏毒性的保护作用及其对凋亡相关基因表达的影响。方法:选取48 hpf的转基因斑马鱼(cmlc2:EGFP)随机分为对照组和不同浓度的DOX和DXXK组,观察药物作用48 h后斑马鱼存活率和心率;DOX(60μM)与DXXK(1,2,4μg·mL^(-1))共处理斑马鱼48h后,体式荧光显微镜的白光条件下观察斑马鱼存活率和心包水肿情况,并计算心包面积和静脉窦-动脉球(SV-BA)距离,荧光条件下记录心脏舒张和收缩过程,计算斑马鱼胚胎心率和搏出量;实时荧光定量PCR检测凋亡相关的基因Bax、Bcl-2和Caspase 3的表达。结果:与正常对照组相比,60μM DOX处理后斑马鱼存活率降低,活动能力减弱,出现明显的心包水肿、心包面积增大以及心房心室重叠面积减少,SV-BA距离变长,心率显著降低(P<0.001),搏出量减少(P<0.01)。而DXXK与阿霉素共处理后存活率得到提高,缓解了斑马鱼心包水肿,心包面积减少,SV-BA距离缩短,心率和搏出量明显增加(P<0.001或P<0.01)。PCR结果显示,DOX组斑马鱼促凋亡基因Bax、Caspase 3的表达明显升高,抗凋亡基因Bcl-2的表达水平降低,而DXXK治疗后逆转上述凋亡基因的表达。结论:地奥心血康对DOX诱导的斑马鱼心脏毒性具有一定的保护作用,可能与影响凋亡相关基因的表达有关。Objective:To investigate the protective effect of Di'ao Xinxuekang(DXXK)against doxorubicin-induced cardiotoxicity in zebrafish and its effect on the expression of apoptosis-related genes.Methods:48 hpf transgenic zebrafish(cmlc2:EGFP)were randomly divided into the control group and the group with different concentrations of DOX and DXXK,to observe the survival and heart rate of the zebrafish after 48 hours of treatment.After co-treatment of zebrafish with DOX(60μM)and DXXK(1,2 and 4μg·mL^(-1))for 48 hours,the survival rate and pericardial oedema of zebrafish were observed under the white light condition of in the fluorescence microscope,and the pericardial area and SV-BA(venous sinus and arterial ball)distance were calculated.The diastolic and systolic processes of the heart were recorded under fluorescence microscopy,and the heart rate and stroke volume(SV)of zebrafish embryos were calculated.RT-qPCR was used to detect the mRNA expressions of Bax,Bcl-2 and Caspase-3.Results:Compared with the control group,DOX treatment decreased survival,reduced mobility,caused pericardial oedema,and increased pericardial area,decreased atrial-ventricular overlap area,and increased SV-BA distance.And DOX decreased heart rate and stroke volume in zebrafish(P<0.001 or P<0.01).In contrast,co-treatment of DXXK with DOX improved the rate of survival,alleviated pericardial oedema,reduced pericardial area,shortened the SV-BA distance,and significantly increased heart rate and SV(P<0.001 or P<0.01).RT-qPCR results showed that DOX significantly increased the mRNA expressions of the pro-apoptotic Bax and Caspase 3,and decreased the mRNA expression of the anti-apoptotic Bcl-2,while the expressions of the above apoptotic genes was reversed by DXXK treatment.Conclusion:DXXK may protect against DOX-induced cardiotoxicity in zebrafish,and this effect may be related to affecting the mRNA expression of apoptosis.

关 键 词：地奥心血康 阿霉素 心脏毒性 斑马鱼 

分 类 号：R285.5[医药卫生—中药学]