Journal of Traditional Chinese Medicine >
Cardioprotective mechanism of Qixuan Yijianing (芪玄抑甲宁) formula in Graves’ disease mice using miRNA sequencing approach
Received date: 2023-09-12
Accepted date: 2023-12-05
Online published: 2024-09-27
Supported by
Research Grant from the National Natural Science Foundation of China: Mechanism Study on the Treatment of Graves' Disease with Yiqi Yangyin Qinggan Sanjie Method based on T helper cell 17 and Related Factors(81302898);Mudanjiang Medical University Research Initiation Fund Project Funding: Mechanism Study on the Treatment of Graves' Disease with Yiqi Yangyin Qinggan Sanjie Method Based on Thyroid Angiogenesis(2023-MYBSKY-008);Funding for the Mudanjiang City Applied Technology Research and Development Program Project: Metabolomics study of extract of Herb of Common Leibnitzia based on Ultra Performance Liquid Chromatography-Time of Flight Mass Spectrometry Technology on Collagen-induced Arthritis Rats(HT2020NS093)
OBJECTIVE: To investigate the mechanism of Qixuan Yijianing (芪玄抑甲宁,QYN) in minimizing cardiac injury in Graves′ disease (GD) mice using microRNA (miRNA) sequencing analysis.
METHODS: Female BALB/c mice were randomly divided into the modeling and control groups (CG). The modeling group was established with Ad-TSHR289. Following 10 weeks of successful modeling, the mice were randomly assigned to four groups: model (MG), methimazole (MMI), QYN low-dose (LD), and high-dose (HD). After four weeks of treatment, the heart rate, heart volume, and heart index were measured, and the levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBD), creatine kinase (CK), and creatine kinase MB isoenzyme (CK-MB) in the serum were detected using a biochemical analyzer. Hematoxylin-eosin and Masson staining were used to determine histological changes in cardiac tissue. The heart tissues in the CG, MG, and HD groups were selected, and miRNA sequencing was used to identify differentially expressed miRNAs. A bioinformatics database was used to predict the target genes of differential miRNAs, and Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted on the predicted target genes.
RESULTS: As compared to the CG group, the MG group's heart rate, heart volume, heart index, AST, CK, CK-MB, LDH, α-HBD, myocardial fiber thickness, and collagen fiber significantly increased, all P < 0.01, while following QYN, these indicators improved in the HD group, all P < 0.01 or P < 0.05. Compared to the CG group, the MG group identified 151 differentially expressed miRNAs, with 42 miRNAs downregulated and 109 miRNAs upregulated; compared to the MG group, the HD group identified 70 differentially expressed miRNAs, 40 were downregulated, and 30 were upregulated. The GO functions of differential miRNA target genes are mostly enriched in cardiac development regulation, cardiac contraction control, heart rate regulation, and so on. The most enriched KEGG pathways include the mitogen-activated protein kinase, ErbB, Hippo, forkhead box protein O, and Wnt signaling pathways.
CONCLUSION: QYN may protect the cardiac structure and function and minimize cardiac damage caused by GD by regulating relevant target genes and signaling pathways through miRNAs which include miR-206-3p, miR-122-5p, and miR-200a-3p.
Changjiu GAO , Song DING , A.D. Mohammed Shadi , Fang LU , Changfeng LIU , Zhan TENG , Peng XU , Shumin LIU . Cardioprotective mechanism of Qixuan Yijianing (芪玄抑甲宁) formula in Graves’ disease mice using miRNA sequencing approach[J]. Journal of Traditional Chinese Medicine, 2024 , 44(6) : 1127 -1136 . DOI: 10.19852/j.cnki.jtcm.20240927.005
| 1. | Ehlers M, Schott M, Allelein S. Graves’ disease in clinical perspective. Front Biosci (Landmark Ed) 2019; 24: 35-47. |
| 2. | Zhang X, Chen L, Sheng J, Li C, He Y, Han W. The association of autoantibodies in hyperthyroid heart disease combined with pulmonary hypertension. Int J Endocrinol 2019; 2019: 9325289. |
| 3. | El-Harasis MA, DeSimone CV, Stan MN, McLeod CJ, Noseworthy PA. Graves' disease-induced complete heart block and asystole. Heart Rhythm Case Rep 2018; 4: 105-8. |
| 4. | Wu L, Wang W, Leng Q, et al. Focus on autoimmune myocarditis in graves' disease: a case-based review. Front Cardiovasc Med 2021; 8: 678645. |
| 5. | Dhital R, Vyas S, Sharma P, Lynn T, Oladiran O, Basnet S. Hyperthyroidism with biventricular heart failure and cirrhotic transformation of the liver. Case Rep Cardiol 2018; 2018: 3861340. |
| 6. | Subekti I, Pramono LA. Current diagnosis and management of graves' disease. Acta Med Indones 2018; 50: 177-82. |
| 7. | Barczyński M. Current approach to surgical management of hyperthyroidism. Q J Nucl Med Mol Imaging 2021; 65: 124-31. |
| 8. | Kahaly GJ. Management of graves thyroidal and extrathyroidal disease: an update. J Clin Endocrinol Metab 2020; 105: 3704-20. |
| 9. | Bartalena L, Piantanida E, Gallo D, Ippolito S, Tanda ML. Management of graves' hyperthyroidism: present and future. Expert Rev Endocrinol Metab 2022; 17: 153-66. |
| 10. | Song E, Kim M, Park S, et al. Treatment modality and risk of heart failure in patients with long-standing graves' disease: a nationwide population-based cohort study. Front Endocrinol (Lausanne) 2021; 12: 761782. |
| 11. | He Q, Dong H, Gong M, et al. New therapeutic horizon of graves' hyperthyroidism: treatment regimens based on immunology and ingredients from Traditional Chinese Medicine. Front Pharmacol 2022; 13: 862831. |
| 12. | Lin CH, Lin CP, Huang ST. Successful intervention with Chinese herbal medicine for hyperthyroidism: two case reports and a literature review. Explore (NY) 2021; 17: 344-50. |
| 13. | Xu W, Jiang Y, Wang N, et al. Traditional Chinese medicine as a promising strategy for the treatment of alzheimer’s disease complicated with osteoporosis. Front Pharmacol 2022; 13: 842101. |
| 14. | Zhang L. Professor Chen Ruquan's academic thoughts and medication rules in the treatment of hyperthyroidism with atrial fibrillation. Wuhan: Hubei University of Chinese Medicine, 2021: 36-8. |
| 15. | Fang JZ. Study on the effect and mechanism of Fufangjiakang tablet on hyperthyroidism rats with cardiac disease. Wuhan: Hubei University of Chinese Medicine, 2006: 32-6. |
| 16. | Correia de Sousa M, Gjorgjieva M, Dolicka D, Sobolewski C, Foti M. Deciphering miRNAs' action through miRNA editing. Int J Mol Sci 2019; 20: 6249. |
| 17. | Henning RJ. Cardiovascular exosomes and microRNAs in cardiovascular physiology and pathophysiology. J Cardiovasc Transl Res 2021; 14: 195-212. |
| 18. | Zhou SS, Jin JP, Wang JQ, et al. miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges. Acta Pharmacol Sin 2018; 39: 1073-84. |
| 19. | Lock MC, Tellam RL, Botting KJ, et al. The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults. J Physiol 2018; 596: 5625-40. |
| 20. | Jin L. The therapeutic effect of miRNA-19a/19b on heart failure in mice and the mechanism of myocardial regeneration and repair. Cell Mol Biol (Noisy-le-grand) 2022; 67: 202-9. |
| 21. | Li G, Shao Y, Guo HC, et al. MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling. Cardiovasc Res 2022; 118: 2139-51. |
| 22. | Ye Q, Liu Q, Ma X, et al. MicroRNA-146b-5p promotes atrial fibrosis in atrial fibrillation by repressing TIMP4. J Cell Mol Med 2021; 25: 10543-53. |
| 23. | Liu SM, Zhen Z, Wang KX, et al. Pharmacodynamic research of Qixuan Yijianing in the treatment of hyperthyroidism. Zhong Yi Yao Xue Bao 2017; 45: 48-51. |
| 24. | Liu SM, Zen Z, Li JY, Xu HY, Wang Y, Liu CF. Regulatory effect of Qixuan Yijianing on Th17 cells of rats with hyperthyroidism. Zhong Yao Yao Li Yu Lin Chuang 2017; 33: 144-8. |
| 25. | Liu SM, Liu CF, Liu XW, Zhang SX. A Traditional Chinese Medicine composition for treating hyperthyroidism and its preparation method and use method. Chinese patent ZL201210460261. 2012 November 15. |
| 26. | Gao CJ, Ding S, Lu F, Liu CF, Yu DH, Liu SM. Discussion of the mechanism of Qixuan Yijianing in the treatment of graves' disease based on network pharmacology and animal experiments. Zhong Guo Yi Yao Dao Bao 2023; 20: 9-14. |
| 27. | Li M, Han B, Zhao H, et al. Biological active ingredients of Astragali Radix and its mechanisms in treating cardiovascular and cerebrovascular diseases. Phytomedicine 2022; 98: 153918. |
| 28. | Zhang X, Qu H, Yang T, Liu Q, Zhou H. Astragaloside IV attenuate MI-induced myocardial fibrosis and cardiac remodeling by inhibiting ROS/caspase-1/GSDMD signaling pathway. Cell Cycle 2022; 21: 2309-22. |
| 29. | Wang Q, Chen W, Yang X, et al. Inhibition of miRNA-1-mediated inflammation and autophagy by astragaloside IV improves lipopolysaccharide-induced cardiac dysfunction in rats. J Inflamm Res 2022; 15: 2617-29. |
| 30. | Zhang CC, Gu WL, Wu XM, Li YM, Chen CX, Huang XY. Active components from Radix Scrophulariae inhibits the ventricular remodeling induced by hypertension in rats. Springerplus 2016; 5: 358. |
| 31. | Lu F, Yu H, Li ZH, Zhang N, Dong WR, Liu SM. Effects of Scrophulariae Radix and split component on isoproterenol-induced ventricular remodeling in rat. Zhong Yao Cai 2016; 39: 863-6. |
| 32. | Gu WL, Chen CX, Huang XY, Gao JP. The effect of angoroside C on pressure overload-induced ventricular remodeling in rats. Phytomedicine 2015; 22: 705-12. |
| 33. | Psotová J, Chlopcíková S, Miketová P, Simánek V. Cytoprotectivity of Prunella vulgaris on doxorubicin-treated rat cardiomyocytes. Fitoterapia 2005; 76: 556-61. |
| 34. | Sun XH. Intrervention effects and mechanisms involved of fritillaria thunbergii extract on the H9c2 myocyte hypertrophy induced by isoprenaline. Hangzhou: Zhejiang University of Technology; 2017: 41-6. |
| 35. | Nile SH, Su J, Wu D, et al. Fritillaria thunbergii Miq. (Zhe Beimu): a review on its traditional uses, phytochemical profile and pharmacological properties. Food Chem Toxicol 2021; 153: 112289. |
| 36. | Wu JR, Guo WX, Zhang XM, Zhang B, Zhang Y. Study on professor Yan Zhenghua's medication regularity in treating heart diseases based on association rules and entropy cluster. Zhong Guo Zhong Yao Za Zhi 2015; 40: 1601-4. |
| 37. | Liu SM, Zhen Z, Wang KX, et al. Pharmacodynamic research of Qixuan Yijianing on treatment for models of graves disease. Liaoning Zhong Yi Yao Da Xue Xue Bao 2018; 20: 5-7. |
| 38. | Li PC, Liu T, Wu Y, Zhang Q, Fu CM, Liu C. Optimization of extraction technology from compound Huanghuai based on coagulation activity and central composite design-response surface methodology. Zhong Guo Zhong Yao Za Zhi 2017; 42: 290-7. |
| 39. | Eckstein A, Philipp S, Goertz G, Banga JP, Berchner-Pfannschmidt U. Lessons from mouse models of graves' disease. Endocrine 2020; 68: 265-70. |
| 40. | The Gene Ontology Consortium. The gene ontology resource: 20 years and still going strong. Nucleic Acids Res 2019; 47: D330-8. |
| 41. | Zhang D, Wang Q, Qiu X, Chen Y, Yang X, Guan Y. Remifentanil protects heart from myocardial ischaemia/reperfusion (I/R) injury via miR-206-3p/TLR4/NF-κB signalling axis. J Pharm Pharmacol 2022; 74: 282-91. |
| 42. | Ge Y, Wang C, Cui B, et al. Isoflurane preconditioning may attenuate cardiomyocyte injury induced by hypoxia/reoxygenation possibly by regulating miR-363-3p. Neurotox Res 2022; 40: 1895-901. |
| 43. | Yang X, Chen G, Chen Z. MicroRNA-200a-3p is a positive regulator in cardiac hypertrophy through directly targeting WDR1 as well as modulating PTEN/PI3K/AKT/CREB/WDR1 signaling. J Cardiovasc Pharmacol 2019; 74: 453-61. |
| 44. | Li L, Wang Q, Yuan Z, et al. Long non-coding RNA H19 contributes to hypoxia-induced CPC injury by suppressing Sirt1 through miR-200a-3p. Acta Biochim Biophys Sin (Shanghai) 2018; 50: 950-9. |
| 45. | Zhang F, Cheng N, Du J, Zhang H, Zhang C. MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis. BMC Cardiovasc Disord 2021; 21: 172. |
| 46. | Shi J, Liu H, Wang H, Kong X. MicroRNA expression signature in degenerative aortic stenosis. Biomed Res Int 2016; 2016: 4682172. |
| 47. | Wang H, Chen Y, Tao T, et al. Identification of microRNA biomarkers in serum of patients at different stages of atrial fibrillation. Heart Lung 2020; 49: 902-8. |
| 48. | Derumeaux GA, d'Humières T. MicroRNA, miR-122-5p, stiffens the diabetic heart. JACC Cardiovasc Imaging 2021; 14: 1143-5. |
| 49. | Song W, Zhang T, Yang N, Zhang T, Wen R, Liu C. Inhibition of micro RNA miR-122-5p prevents lipopolysaccharide-induced myocardial injury by inhibiting oxidative stress, inflammation and apoptosis via targeting GIT1. Bioengineered 2021; 12: 1902-15. |
| 50. | Peng H, Luo Y, Ying Y. LncRNA XIST attenuates hypoxia-induced H9c2 cardiomyocyte injury by targeting the miR-122-5p/FOXP2 axis. Mol Cell Probes 2020; 50: 101500. |
| 51. | Song J, Zhang Z, Dong Z, et al. MicroRNA-122-5p aggravates angiotensin II-mediated myocardial fibrosis and dysfunction in hypertensive rats by regulating the elabela/apelin-APJ and ACE2-GDF15-porimin signaling. J Cardiovasc Transl Res 2022; 15: 535-47. |
| 52. | Geng H, Chen L, Su Y, et al. miR-431-5p regulates apoptosis of cardiomyocytes after acute myocardial infarction via targeting selenoprotein T. Physiol Res 2022; 71: 55-62. |
| 53. | Xu Z, Sun J, Tong Q, et al. The role of ERK1/ 2 in the development of diabetic cardiomyopathy. Int J Mol Sci 2016; 17: 2001. |
| 54. | Turner NA, Blythe NM. Cardiac fibroblast p38 MAPK: a critical regulator of myocardial remodeling. J Cardiovasc Dev Dis 2019; 6: 27. |
| 55. | Romero-Becerra R, Santamans AM, Folgueira C, Sabio G. P38 MAPK pathway in the heart: new insights in health and disease. Int J Mol Sci 2020; 21: 7412. |
| 56. | Luo Y, Jiang N, May HI, et al. Cooperative binding of ETS2 and NFAT links Erk1/2 and calcineurin signaling in the pathogenesis of cardiac hypertrophy. Circulation 2021; 144: 34-51. |
| 57. | Ai X, Yan J, Carrillo E, Ding W. The stress-response MAPK inase signaling in cardiac arrhythmias. Rev Physiol Biochem Pharmacol 2016; 172: 77-100. |
| 58. | Galindo CL, Ryzhov S, Sawyer DB. Neuregulin as a heart failure therapy and mediator of reverse remodeling. Curr Heart Fail Rep 2014; 11: 40-9. |
| 59. | Vermeulen Z, Hervent AS, Dugaucquier L, et al. Inhibitory actions of the NRG-1/ErbB4 pathway in macrophages during tissue fibrosis in the heart, skin, and lung. Am J Physiol Heart Circ Physiol 2017; 313: H934-45. |
| 60. | Nakagawa A, Naito AT, Sumida T, et al. Activation of endothelial β-catenin signaling induces heart failure. Sci Rep 2016; 6: 25009. |
| 61. | Missinato MA, Saydmohammed M, Zuppo DA, et al. Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration. Development 2018; 145: 157206. |
| 62. | Shiraishi M, Yamaguchi A, Suzuki K. Nrg1/ErbB signaling-mediated regulation of fibrosis after myocardial infarction. Faseb J 2022; 36: e22150. |
| 63. | Wang J, Liu S, Heallen T, Martin JF. The Hippo pathway in the heart: pivotal roles in development, disease, and regeneration. Nat Rev Cardiol 2018; 15: 672-84. |
| 64. | Xie J, Wang Y, Ai D, Yao L, Jiang H. The role of the Hippo pathway in heart disease. Febs J 2022; 289: 5819-33. |
| 65. | Chen X, Li Y, Luo J, Hou N. Molecular mechanism of Hippo-YAP1/TAZ pathway in heart development, disease, and regeneration. Front Physiol 2020; 11: 389. |
| 66. | Meng F, Xie B, Martin JF. Targeting the Hippo pathway in heart repair. Cardiovasc Res 2022; 118: 2402-14. |
| 67. | Hou N, Wen Y, Yuan X, et al. Activation of Yap1/Taz signaling in ischemic heart disease and dilated cardiomyopathy. Exp Mol Pathol 2017; 103: 267-75. |
| 68. | Mia MM, Singh MK. The Hippo signaling pathway in cardiac development and diseases. Front Cell Dev Biol 2019; 7: 211. |
| 69. | Xin Z, Ma Z, Jiang S, et al. FOXOs in the impaired heart: new therapeutic targets for cardiac diseases. Biochim Biophys Acta Mol Basis Dis 2017; 1863: 486-98. |
| 70. | Samanta J, Mondal A, Saha S, Chakraborty S, Sengupta A. Oleic acid protects from arsenic-induced cardiac hypertrophy via AMPK/FoxO/NFATc3 pathway. Cardiovasc Toxicol 2020; 20: 261-80. |
| 71. | Spurthi KM, Sarikhani M, Mishra S, et al. Toll-like receptor 2 deficiency hyperactivates the FoxO1 transcription factor and induces aging-associated cardiac dysfunction in mice. J Biol Chem 2018; 293: 13073-89. |
| 72. | Gong Y, Yang J, Liu Q, et al. IGF1 knockdown hinders myocardial development through energy metabolism dysfunction caused by ROS-dependent FOXO activation in the chicken heart. Oxid Med Cell Longev 2019; 2019: 7838754. |
| 73. | Akoumianakis I, Polkinghorne M, Antoniades C. Non-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications. Nat Rev Cardiol 2022; 19: 783-97. |
| 74. | Liu Y, Neogi A, Mani A. The role of Wnt signalling in development of coronary artery disease and its risk factors. Open Biol 2020; 10: 200128. |
| 75. | Hu HH, Cao G, Wu XQ, Vaziri ND, Zhao YY. Wnt signaling pathway in aging-related tissue fibrosis and therapies. Ageing Res Rev 2020; 60: 101063. |
| 76. | Lyu X, Li J, Hu Y, et al. Overexpression of miR-27b-3p targeting wnt3a regulates the signaling pathway of Wnt/β-catenin and attenuates atrial fibrosis in rats with atrial fibrillation. Oxid Med Cell Longev 2019; 2019: 5703764. |
| 77. | Wei F, Ren B, Han W, Guan H, Jing G, Wang M. Investigate the effect of miR-22 on the apoptosis of coronary heart disease cells through the Wnt-1 pathway based on nano-silica-induced rat models. J Nanosci Nanotechnol 2021; 21: 1338-44. |
| 78. | Methatham T, Tomida S, Kimura N, Imai Y, Aizawa K. Inhibition of the canonical Wnt signaling pathway by a β-catenin/CBP inhibitor prevents heart failure by ameliorating cardiac hypertrophy and fibrosis. Sci Rep 2021; 11: 14886. |
/
| 〈 |
|
〉 |