康达心口服液对阿霉素诱导的斑马鱼心脏毒性保护作用的研究

Study on the Protective Effect of Kangda Xin Oral Liquid against Doxorubicin-induced Cardiotoxicity in Zebrafish

目的:评估康达心口服液对阿霉素诱导的斑马鱼心脏毒性的保护作用,并探讨其潜在的保护机制。方法:将实验分为空白对照组、阿霉素造模组、康达心低浓度组、康达心中浓度组和康达心高浓度组。设计阿霉素和康达心口服液浓度梯度,筛选出35μg·mL^(-1)的阿霉素作为诱导浓度,5.9325×10^(-2)μg·mL^(-1)、11.875×10^(-2)μg·m L^(-1)和23.75×10^(-2)μg·m L^(-1)的康达心口服液分别作为低浓度、中浓度和高浓度治疗浓度。定时统计斑马鱼的破膜率和死亡率;通过显微镜观察斑马鱼的畸形和心率等情况;通过TUNEL荧光观察心肌细胞的凋亡情况;JC–1处理评估线粒体膜电位(MMP);检测活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH–Px)分析氧化损伤。结果:与空白对照组比较,阿霉素造模组和康达心低浓度组斑马鱼心率显著下降,而康达心中浓度组和高浓度组斑马鱼心率显著升高,差异均具有统计学意义(P<0.05);荧光染色显示,与空白对照组比较,阿霉素造模组心肌细胞凋亡和线粒体损伤均升高,康达心口服液共处理有效缓解了细胞凋亡和线粒体损伤。结论:康达心口服液对阿霉素诱导的斑马鱼心脏毒性具有保护作用。

Objective To evaluate the protective effect of Kangda Xin oral liquid on doxorubicin-induced cardiotoxicity in zebrafish and to explore its potential protective mechanisms.Methods The experiment was divided into blank control group,doxorubicin model group,Kangda Xin low-concentration group,Kangda Xin medium-concentration group,and Kangda Xin highconcentration group.Doxorubicin and Kangda Xin concentration gradients were designed,with 35μg·mL^(-1) doxorubicin as the inducing concentration,and 5.9325×10^(-2)μg·mL^(-1),11.875×10^(-2)μg·mL^(-1),and 23.75×10^(-2)μg·mL^(-1) Kangda Xin as the low,medium,and high therapeutic concentrations,respectively.The rates of hatching and mortality in zebrafish were statistically analyzed at regular intervals.The malformations and heart rates of zebrafish were observed under a microscope.The cardiac cell apoptosis was observed by TUNEL fluorescence.JC-1 treatment was used to evaluate mitochondrial membrane potential(MMP).Oxidative damage was analyzed by detecting reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px).Results Compared with the blank control group,the heart rates of zebrafish in the doxorubicin model group and the Kangda Xin low-concentration group significantly decreased,while the heart rates in the Kangda Xin medium and highconcentration groups significantly increased,with statistically significant differences(P<0.05).Fluorescence staining showed that compared with the blank control group,the apoptosis of cardiac cells and mitochondrial damage were increased in the doxorubicin induced model group,and the co-treatment with Kangda Xin oral liquid effectively alleviated cell apoptosis and mitochondrial damage. Conclusion Kangda Xin oral liquid has a protective effect against doxorubicin-induced cardiotoxicity in zebrafish.