Artemisinin suppresses myocardial ischemia–reperfusion injury via NLRP3 inflammasome mechanism
Autor: | Qianping Gao, Zhixin Fan, Lu Fu, Fengyue Wang, Jing Yang, Junxian Cao, Junfeng Sun, Can Wang |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Cardiac function curve Inflammasomes Clinical Biochemistry Myocardial Ischemia Apoptosis Myocardial Reperfusion Injury Pharmacology Antimalarials 03 medical and health sciences 0302 clinical medicine NLR Family Pyrin Domain-Containing 3 Protein parasitic diseases Autophagy medicine Animals Myocardial infarction Artemisinin Molecular Biology TUNEL assay integumentary system business.industry Inflammasome Cell Biology General Medicine medicine.disease Artemisinins Rats 030104 developmental biology 030220 oncology & carcinogenesis business Reperfusion injury Signal Transduction medicine.drug |
Zdroj: | Molecular and Cellular Biochemistry. 474:171-180 |
ISSN: | 1573-4919 0300-8177 |
Popis: | Artemisinin is known for its pharmaceutical effect against malaria and received increased attention for its other potential function. Mounting evidence suggest that artemisinin could also exert cardioprotective effects while the understanding of its regulatory mechanism is still limited. This study is designed to investigate the role of artemisinin in myocardial ischemia/reperfusion (I/R) injury and the involvement of NLRP3 inflammasome. Artemisinin was administrated for 14 consecutive days intragastrically before I/R injury. Cardiac function was assessed by echocardiography. Infarct area was observed through HE and TTC staining. Apoptosis and autophagy were assessed by TUNEL and Western blotting. The artemisinin-treated myocardial I/R rats demonstrated less severe myocardial I/R injury (smaller infarct size and lower CK-MB, LDH), significant inhibition of cardiac autophagy (decreased LC3II/I and increased p62), improved mitochondrial electron transport chain activity, concomitant with decreased activation of NLRP3 inflammasome (decreased NLRP3, ASC, cleaved caspase-1, IL-1β). In conclusion, our findings further confirmed that activation of the NLRP3 inflammasome pathway is involved in myocardial I/R injury, whereas artemisinin preconditioning could effectively protect against myocardial I/R injury through suppression of NLRP3 inflammasome activation. Therefore, the NLRP3 inflammasome might serve as a promising therapeutic target providing new mechanisms for understanding the effect of artemisinin during the evolution of myocardial infarction. |
Databáze: | OpenAIRE |
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