Qishen Granules Attenuate Doxorubicin-induced Cardiotoxicity via TBC1D15-mediated Mitochondria-lysosome Contacts
10.13422/j.cnki.syfjx.20260207
- VernacularTitle:基于TBC1D15介导的线粒体-溶酶体接触探讨芪参颗粒改善阿霉素心脏损伤的机制
- Author:
Nannan TAN
1
;
Weili LI
1
;
Guanjing LING
1
;
Yan WEI
1
;
Linghui LU
1
;
Yong WANG
1
Author Information
1. School of Traditional Chinese Medicine， Beijing University of Chinese Medicine， Beijing 100020，China
- Publication Type:Journal Article
- Keywords:
Qishen granules;
cardio-oncology disease;
mitochondria-lysosome contact （MLC）;
autophagy;
TBC1 domain family member 15 （TBC1D15）;
cardiotoxicity
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(21):99-109
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo verify the protective effect and pharmacological mechanism of Qishen granules against doxorubicin-induced cardiotoxicity， thus providing a basis for developing new drug options for clinical treatment of cardio-oncology disease. MethodsFifty mice were randomly assigned into a normal group （n=10） and a modeling group （n=40）. The model was established by intravenous injection of doxorubicin （5 mg·kg-1） via the tail vein， once a week for 4 consecutive weeks. The normal group was injected with an equal volume of normal saline during the same period. The modeled mice were further assigned into four groups： doxorubicin （no drug control）， low-dose （3.33 mg·kg-1） Qishen granules， high-dose （6.67 mg·kg-1） Qishen granules， and enalapril （15 mg·kg-1）. Mice were administrated with corresponding drugs by gavage for 4 consecutive weeks. At the end of the experiment， echocardiography， histopathological staining， and live-cell imaging were employed to determine relevant indicators， on the basis of which the protective effect of Qishen granules against doxorubicin-induced cardiotoxicity was evaluated. ResultsCompared with the normal group， doxorubicin treatment reduced the left ventricular ejection fraction （LVEF） （P<0.05） and caused pathological changes including disarrangement of cardiomyocytes， increased cell spacing， cardiomyocyte hypertrophy， and increased apoptosis in the heart tissue. Meanwhile， doxorubicin prolonged the mitochondria-lysosome contact time， downregulated the expression of TBC1 domain family member 15 （TBC1D15） （P<0.01）， upregulated the levels of microtubule-associated protein 1 light chain 3 （LC3） and sequestosome 1 （p62） （P<0.01）， and induced mitochondrial cristae breakage， resulting in mitochondrial dysfunction. Compared with the doxorubicin group， intervention with Qishen granules reversed the above indicators. It not only increased the LVEF （P<0.01） and alleviated pathological damage to the heart， but also upregulated the expression of TBC1D15 （P<0.01）， shortened the mitochondria-lysosome contact time （P<0.05）， and downregulated the protein levels of LC3 and p62. When TBC1D15 in cells was knocked down， the autophagy-activating and mitochondrion-protecting effects of Qishen granules partially disappeared. ConclusionQishen granules upregulate the expression of TBC1D15 to shorten the mitochondria-lysosome contact time， thereby activating autophagy and ultimately exerting a protective effect against doxorubicin-induced cardiotoxicity.
