Affiliation:
1. Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
2. Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing, China
3. Department of Pathophysiology, Chinese PLA General Hospital, Beijing, China
Abstract
Objective. Modified Si-Miao-Yong-An decoction (MSMYA) was empirically originated from Si-Miao-Yong-An Decoction, which has been utilized for centuries to treat vasculopathy as well as heart diseases through clearing heat and detoxifying. This study aimed at confirming MSMYA’s therapeutic effects for treating myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms. Methods. Rats were intragastrically administered with MSMYA for 4 weeks after ischemia/reperfusion (I/R) operation. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentration were determined by calorimetry. Coagulation function was determined using an automated coagulation analyzer. Levels of cysteinyl aspartate specific proteinase (caspase)-1, interleukin (IL)-1β, interleukin (IL)-18, and lactate dehydrogenase (LDH) were measured by an enzyme-linked immunosorbent assay (ELISA). Infarct size was determined by triphenyltetrazolium chloride (TTC) staining. Myocardial histopathological and ultrastructure changes were examined by H&E staining and electron microscopy, respectively. Relative mRNA expression of NLRP3, an apoptosis-associated speck-like proteins containing the caspase activation and recruitment domain (ASC), caspase-1, IL-1β, and IL-18 were analyzed using quantitative real-time polymerase chain reaction (PCR). Meanwhile, their relative protein expressions were measured using western blotting. Results. The results showed MSMYA can inhibit oxidative stress by increasing SOD and reducing MDA, suppress inflammatory reaction by decreasing NLRP3 inflammasome-related cytokines’ level, improve coagulation function by increasing prothrombin time (PT) and activating partial thromboplastin time (APTT), and ameliorate myocardial histopathological and ultrastructural changes. In addition, MSMYA’s cardioprotective effects probably related to suppressing NLRP3 inflammasome pathway activation by reducing NLRP3 inflammasome molecular mRNA and protein relative expression. Conclusion. The results indicated that MSMYA played an important role in protecting the myocardium from I/R injury. The likely mechanism is the inhibition of oxidative stress, improvement of cardiac injury, and the reduction of NLRP3-related inflammatory cytokines release. This provides a basis for further research on the mechanism and clinical application of MSMYA to improve myocardial I/R injury.
Funder
National Natural Science Foundation of China
Subject
Complementary and alternative medicine
Reference25 articles.
1. Effects of percutaneous coronary intervention on death and myocardial infarction stratified by stable and unstable coronary artery disease: a meta-analysis of randomized controlled trials;C. Liza;Circilation Cardiovascular Quality and Outcomes,2020
2. A review of myocardial ischaemia/reperfusion injury: pathophysiology, experimental models, biomarkers, genetics and pharmacological treatment;G. Mehmet;Cell Biochemistry and Function,2021
3. Psychological Stress, Inflammation, and Coronary Heart Disease
4. Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury;T. Stefano;American Journal of Physiology. Heart and Circulatory Physiology,2018
5. NLRP3 Is Involved in Ischemia/Reperfusion Injury
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献