基于斑马鱼模型研究康达心口服液对阿霉素心脏毒性的预防和作用机制  

Prevention and mechanism of Kangdaxin oral liquid on Doxorubicin-induced cardiotoxicity based on zebrafish

作　　者：乔建峰[1] 熊尚全[1] 林超[1] 王婷[1] 何顺勇[1] QIAO Jianfeng;XIONG Shangquan;LIN Chao;WANG Ting;HE Shunyong(The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou 350004,China)

机构地区：[1]福建中医药大学附属人民医院,350004

出　　处：《中国老年保健医学》2024年第5期38-43,共6页Chinese Journal of Geriatric Care

基　　金：福建省自然科学基金项目(编号:2020J011050),福建省名老中医专家传承工作室建设项目(编号:闽卫中医函[2023]697号)。

摘　　要：目的基于斑马鱼模型探究复方中药康达心口服液对阿霉素(doxorubicin,DOX)所致心脏毒性的预防及作用机制。方法将实验对象分为空白对照组、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浓度梯度,筛选出35μg/mL的阿霉素作为诱导浓度,5.9325×10^(-2)μg/mL、11.875×10^(-2)μg/mL和23.75×10^(-2)μg/mL的康达心分别作为低浓度、中浓度和高浓度治疗浓度。显微镜观察斑马鱼的畸形和心率等情况;TUNEL荧光观察心脏细胞的凋亡情况;Q-PCR和Western blot检测心脏发育相关基因及蛋白(SOX9b、GATA4、NKX2.5)的表达和凋亡相关基因及蛋白(P53、Caspase-9、bcl2、Bax、TNF-α)的表达。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(P<0.05),而康达心中浓度组和高浓度组斑马鱼心率显著升高(P<0.05);荧光染色显示,与空白对照组比较,阿霉素造模组心脏细胞凋亡升高(P<0.05),不同浓度康达心共处理组心脏细胞凋亡显著降低(P<0.05);Q-PCR和Western blot检测显示,与空白对照组比较,阿霉素造模组心脏发育相关基因及蛋白表达、凋亡相关基因表达显著下降(P<0.05);与阿霉素造模组比较,不同浓度康达心处理组使心脏发育相关基因及蛋白表达、凋亡相关基因表达升高(P<0.05)。结论康达心口服液对阿霉素诱导的心脏毒性具有显著的预防作用,对心肌具有保护作用,也为其临床应用提供了科学依据。Objective Prevention and mechanism of Kangdaxin Oral Liquid on Doxorubicin-induced cardiotoxicity based on zebrafish.Methods The experimental subjects was divided into a blank control group,an Doxorubicin modelling group,a Kangdaxin low concentration group,a Kangdaxin concentration group and a Kangdaxin high concentration group.The concentration gradient of Doxorubicin and Kandaxin was designed,and 35μg/mL of Doxorubicin was screened as the induction concentration,and 5.9325×10^(-2)μg/mL、11.875×10^(-2)μg/mL和23.75×10^(-2)μg/mL of Kandaxin as the low,final,and high therapeutic concentrations.The deformity and heart rate of zebrafish were observed by microscope;the apoptosis of cardiac cells was observed by TUNEL fluorescence.Expression of cardiac development-related genes and proteins(SOX9b,GATA4,NKX2.5)and apoptosis-associated genes and proteins(P53,casp9,bcl2,Bax,TNF-α)by RT-qPCR and Western blotting expression.Results Compared with the blank control group,the heart rate of zebrafish in the Adriamycin modelling group and the low concentration group of Kangdaxin significantly decreased(P<0.05),while the heart rate of zebrafish in the concentration group of Kangdaxin and the high concentration group of Kangdaxin significantly increased(P<0.05).Fluorescence staining showed that compared with the blank control group,the apoptosis of cardiac cells in the Doxorubicin modelling group was increased(P<0.05),while the apoptosis of cardiac cells in the Kangdaxin co-treatment group at different concentrations was significantly reduced(P<0.05);Q-PCR and Western blot analysis showed that compared with the blank control group,the expression of heart development related genes and proteins,as well as apoptosis related genes,significantly decreased in the Doxorubicin induced model group(P<0.05);Compared with the Doxorubicin modelling group,different concentrations of Kangdaxin co-treatment group increased the expression of heart development related genes and proteins,as well as apoptosis related genes(P<0.05).Conclusio

关 键 词：康达心口服液 心脏毒性 阿霉素 斑马鱼模型 心脏保护 

分 类 号：R285.5[医药卫生—中药学]