RNA-Seq Profiling to Investigate the Mechanism of Qishen Granules on Regulating Mitochondrial Energy Metabolism of Heart Failure in Rats
Hao He
School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorChangxiang Li
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorXiangyu Lu
Modern Research Center of Traditional Chinese Medicine, School of Traditional Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorYanqin Li
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorXuan Li
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorXiaoqian Sun
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorCorresponding Author
Binghua Tang
School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorCorresponding Author
Yan Wu
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Beijing Key Laboratory of TCM Syndrome and Formula, Beijing, China
Search for more papers by this authorCorresponding Author
Chun Li
Modern Research Center of Traditional Chinese Medicine, School of Traditional Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Key Laboratory of TCM Syndrome and Formula (Beijing University of Chinese Medicine), Ministry of Education, Beijing, China meb.gov.tr
Search for more papers by this authorHao He
School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorChangxiang Li
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorXiangyu Lu
Modern Research Center of Traditional Chinese Medicine, School of Traditional Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorYanqin Li
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorXuan Li
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorXiaoqian Sun
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorCorresponding Author
Binghua Tang
School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Search for more papers by this authorCorresponding Author
Yan Wu
College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Beijing Key Laboratory of TCM Syndrome and Formula, Beijing, China
Search for more papers by this authorCorresponding Author
Chun Li
Modern Research Center of Traditional Chinese Medicine, School of Traditional Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China bucm.edu.cn
Key Laboratory of TCM Syndrome and Formula (Beijing University of Chinese Medicine), Ministry of Education, Beijing, China meb.gov.tr
Search for more papers by this authorAbstract
Background. Qishen granules (QSG) are a frequently prescribed formula with cardioprotective properties prescribed to HF for many years. RNA-seq profiling revealed that regulation on cardiac mitochondrial energy metabolism is the main therapeutic effect. However, the underlying mechanism is still unknown. In this study, we explored the effects of QSG on regulating mitochondrial energy metabolism and oxidative stress through the PGC-1α/NRF1/TFAM signaling pathway. RNA-seq technology revealed that QSG significantly changed the differential gene expression of mitochondrial dysfunction in myocardial ischemic tissue. The mechanism was verified through the left anterior descending artery- (LAD-) induced HF rat model and oxygen glucose deprivation/recovery- (OGD/R-) established H9C2 induction model both in vivo and in vitro. Echocardiography and HE staining showed that QSG could effectively improve the cardiac function of rats with myocardial infarction in functionality and structure. Furthermore, transcriptomics revealed QSG could significantly regulate mitochondrial dysfunction-related proteins at the transcriptome level. The results of electron microscopy and immunofluorescence proved that the mitochondrial morphology, mitochondrial membrane structural integrity, and myocardial oxidative stress damage can be effectively improved after QSG treatment. Mechanism studies showed that QSG increased the expression level of mitochondrial biogenesis factor PGC-1α/NRF1/TFAM protein and regulated the balance of mitochondrial fusion/fission protein expression. QSG could regulate mitochondrial dysfunction in ischemia heart tissue to protect cardiac function and structure in HF rats. The likely mechanism is the adjustment of PGC-1α/NRF1/TFAM pathway to alleviate oxidative stress in myocardial cells. Therefore, PGC-1α may be a potential therapeutic target for improving mitochondrial dysfunction in HF.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
Open Research
Data Availability
The data used to support the findings of this study are available from the corresponding author upon request.
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