Journal
ATHEROSCLEROSIS
Volume 231, Issue 2, Pages 384-391Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2013.10.003
Keywords
Coptisine; Ischemia/reperfusion (I/R); Apoptosis; Inflammation; Rho-kinase (ROCK)
Funding
- National Scientific & Technological major special project significant creation of new drugs [2013ZX09103-001-008, 2012ZX09103-101-078]
- Special Foundation on Scientific and Technological basic work [2007FY130100]
- National Natural Science Foundation of China [81102444, 81202538, 81373269]
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Objective: Protecting the heart from myocardial ischemia and reperfusion (I/R) damage is the focus of intense research. Coptisine is an isoquinoline alkaloid isolated from Coptidis Rhizoma. The present study investigated the potential effect of coptisine on myocardial I/R damage in rats and the underlying mechanisms. Methods and results: Electrocardiogram examination showed that the administration of coptisine 10 min before ischemia significantly decreased I/R-induced arrhythmia after 30 min ischemia followed by 3 h reperfusion. The release of cardiac markers was also limited. Echocardiography was performed before ischemia and 24 h post-I/R, separately. The M-mode records showed that the reductions of ejection fraction (EF) and fractional shortening (FS) were attenuated in coptisine-treated rats compared with the I/R rats. Similar results were obtained with Evans Blue/triphenyl tetrazolium chloride (TTC) staining, in which coptisine notably reduced infarct size. Moreover, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated coptisine suppressed myocardial apoptosis, which may be related to the upregulation of Bcl-2 protein and inhibition of caspase-3 activation. Coptisine treatment also attenuated the proinflammatory cytokines including interleukin (IL)-1 therefore beta, IL-6, and tumor necrosis factor-a in heart tissue. Additionally, Western blot and immunohistochemical analysis showed that coptisine markedly reduced Rho, Rho-kinase 1 (ROCK1), and ROCK2 expression and attenuated the phosphorylation of myosin phosphatase targeting subunit-1, a downstream target of ROCK. Conclusions: Coptisine exerts pronounced cardioprotection in rats subjected to myocardial I/R likely through suppressing myocardial apoptosis and inflammation by inhibiting the Rho/ROCK pathway. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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