Prevention and Mechanism of Huoxin Pill on Doxorubicin-Induced Cardiotoxicity Based on Zebrafish
Objective:To discuss the protective effect and mechanism of Huoxin pill(HXP)on doxorubicin(DOX)induced car-diotoxicity in zebrafish model.Methods:Eighty wild-type AB strain female zebrafish were randomly divided into control group,mod-el group,low-dose group and high-dose group,with 20 zebrafish in each group.On the 1st to 7th day,the low-and high-dose groups were intraperitoneally injected with HXP solution at the dose of 9 and 12 μg/(g·d),respectively,and the control and model groups were intraperitoneally injected with normal saline at the dose of 5.7 μL/(g·d).On the 8th day,the model,low-dose and high-dose groups were intraperitoneally injected with DOX solution at the dose of 20 μg/(g·d),and the control group was intraperitoneally inject-ed with normal saline at the dose of 5.7 μL/(g·d).The survival of zebrafish in each group was observed every 7 days after DOX injec-tion.After 4 weeks of DOX injection,ventricular area and ventricular area/body weight were measured.Masson staining was used to observe the degree of myocardial tissue fibrosis;α-actinin immunofluorescence staining was used to observe the arrangement of myo-cardium;Tunel staining was used to observe the apoptosis of myocardial tissue;qPCR was used to detect the mRNA expression level of prostaglandin-endoperoxide synthase 2(ptgs2),arachidonate 5-lipoxygenase(alox5a),NADPH oxidase 1(nox1),glutathione perox-idases 1(gpx1),atrial natriuretic factor(anf),tumor necrosis factor α(tnfα),interleukin 6(il6),and transforming growth factor β1b(tgfβ1b)in cardiac tissue.Results:Compared with the control group,the ventricular area and ventricular area/body weight in the model group significantly increased(P<0.05);the mRNA expression level of ptgs2,alox5a,nox1,anf,tnfα,and il6 significantly increased(P<0.05),while the mRNA expression level of gpx1 significantly decreased(P<0.05);pathology showed myocardial hypertrophy,adhesion,fibrosis,disordered arrangement of myocardial tissue,and increased apoptotic cells.Compared with the model group,the ventricular area and ventricular area/body weight in the high-dose group significantly decreased(P<0.05);the mRNA expression level of ptgs2,alox5a,nox1,anf,tnfα,and il6 significantly decreased(P<0.05),while mRNA expression level of tgfβ1b and gpx1 sig-nificantly increased(P<0.05);pathology showed improvement in myocardial hypertrophy,adhesion,fibrosis,disordered arrangement of myocardial tissue,and cell apoptosis.Conclusion:HXP can effectively prevent pathological changes in zebrafish heart caused by doxorubicin,and its mechanism may be related to down-regulating ferroptosis and inflammation level.
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