Study on Myocardial Lymphangiogenesis Disorder in Dilated Cardiomyopathy Mice Induced by Doxorubicin and the Protective Mechanism of Kuoxin Decoction
- VernacularTitle:阿霉素诱导扩张型心肌病模型小鼠心脏淋巴管生成障碍及扩心方干预作用的研究
- Author:
Yidan DONG
1
;
Mengjiao MA
;
Longping PENG
;
Maolin ZHOU
;
Qianqian LIANG
;
Qiong WU
;
Yanwen WANG
;
Youhua WANG
Author Information
- Keywords: Dilated cardiomyopathy; Lymphangiogenesis; Kuoxin decoction; Doxorubicin; Cardiac function
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(10):3293-3303
- CountryChina
- Language:Chinese
- Abstract: Objective To observe the dynamic changes of cardiac lymphangiogenesis in Doxorubicin(DOX)-induced dilated cardiomyopathy(DCM)model mice,and to study the the protective mechanism of Kuoxin Decoction.Methods The DCM mouse model was established by intraperitoneal injection of DOX,and the dynamic observation was performed every week.On this basis,60 C57BL/6 mice were randomly divided into 6 groups(n=10):control group,Model group,L-KXD,M-KXD and H-KXD groups and Captopril group.After successful modeling,the KXD and the positive control drug Captopril were administered continuously for 28 days.Echocardiography was used to detect cardiac function in mice,HE staining and Masson staining were used to observe pathological and morphological changes of the heart,Whole-mount immunofluorescent staining was used to detect the expression of LYVE-1 and Podoplanin in epicardial lymphatic vessels,Western blot was used to detect the expression of VEGFR-3 protein,and qPCR was used to detect the expression of VEGFR-3 mRNA.Results DCM mice induced by DOX showed significant cardiac function decline from the third week(DOX:15 mg·kg-1,P<0.05),and significant ventricular remodeling at the fifth week(DOX:15 mg·kg-1,P<0.01);The lymphatic vessel area of the mouse heart decreased significantly from the fourth week(DOX:20 mg·kg-1,P<0.0001),and the expression of VEGFR-3 decreased significantly from the third week(DOX:15 mg·kg-1,P<0.01).Conclusion KXD can improve ventricular remodeling and cardiac function in DOX-induced DCM mice,promote cardiac lymphangiogenesis,and upregulate the expression of VEGFR-3 at protein and mRNA levels,with a better effect than captopril.DOX-induced cardiac lymphangiogenesis in DCM mice leads to severe myocardial fibrosis and weakened cardiac function,which gradually worsens with the accumulation of modeling time and dose.KXD can promote cardiac lymphangiogenesis and improve cardiac function in DOX-induced DCM mice.The mechanism may be related to the up-regulation of VEGFR-3 expression.
