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DOI: 10.1055/s-0043-1770075
Mitophagy Regulation by Kangxian Yixin Granule in a Mouse Model of Dilated Cardiomyopathy
Funding This study was funded by the Science and Technology Project of Henan Province (212102310368).Abstract
Objective Kangxian Yixin granule (KXYXG) has been found to be effective in the clinical treatment of dilated cardiomyopathy (DCM). We aim to explore the effect of KXYXG and the underlying mechanism in a mouse model of DCM.
Methods Thirty specific pathogen-free (SPF) male cTnTR141W mice with DCM were randomly divided into the model group, KXYXG (20.4 g/kg/d) group and coenzyme Q10 (CoQ10) (1.5 mg/kg/d) group; 10 SPF male C57BL/6J mice were included to form the normal group. The mice in KXYXG group and CoQ10 group were administered by oral gavage for 8 weeks. M-echocardiography was used to evaluate the cardiac function in mice, and hematoxylin and eosin staining and transmission electron microscopy were performed to observe morphological characters. The colocalization and expression levels of mitophagy-related proteins were observed using immunofluorescence and western blot.
Results Compared with the normal group, the model group showed ventricular remodeling, cardiac insufficiency, disordered arrangement of cardiomyocytes, as well as disordered mitochondria and irregular and diffuse swelling. Furthermore, the model group had lower mitophagy protein colocalization and autophagy flux. Furthermore, PINK1 and Parkin expression levels decreased in the mice with DCM (p < 0.05). KXYXG could decrease the left ventricular end-diastolic and end-systolic diameters and mitochondrial injury, rescue cardiac dysfunction and remodeling, and protect against myocardial ultrastructure changes in the mice with DCM. KXYXG also increased the colocalization levels of mitophagy-related proteins and PINK1 and Parkin expression levels compared with those in the model group (p < 0.05).
Conclusion KXYXG can protect against heart injury by possibly activating the PINK1/Parkin pathway and mitophagy in mice with DCM.
Keywords
dilated cardiomyopathy - mitophagy - Kangxian Yixin Granule - PINK1/Parkin pathway - Chinese medicine - heart failureCRediT Authorship Contribution Statement
S.L.: conceptualization, data curation, formal analysis, writing—original draft. X.H.: data curation, resources. H.W.: writing—review and editing. Z.W.: conceptualization, data curation, software, project administration.
Publication History
Received: 13 October 2022
Accepted: 20 November 2022
Article published online:
28 June 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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