Resina draconis inhibits the endoplasmic-reticulum-induced apoptosis of myocardial cells via regulating miR-423-3p/ERK signaling pathway in a tree shrew myocardial ischemia– reperfusion model

ABSTRACT

Ischemia-reperfusion (IR) is one of the significant medical problems in China. Triphenyltetrazolium chloride (TTC) stainingis used to detect the status of the infarct size, and real-time PCR and western blotting are used to detect expressions ofgenes. TUNEL assay has been used to detect apoptosis. Using a tree shrew myocardial IR model, we found that in thereperfusion period, resina draconis (RD) treatment reduced the infarct size by TTC staining, and significantly enhanced thesuperoxide dismutase expression and down-regulated the malondialdehyde concentration in a dose-dependent manner. Inhearts showing IR, Bax was increased and Bcl-2 was reduced, and RD treatment inhibited the IR-induced Bax expressionand up-regulated the IR suppressed level of Bcl-2. TUNEL assay showed that IR induced the apoptosis of myocardial cells,and RD treatment suppressed the IR-induced apoptosis. CHOP and GRP78 were also upregulated in IR hearts, and RDtreatment could significantly attenuate the CHOP and GRP78 levels compared with IR group. We further found that IRdecreased the miR-423-3p expression and upregulated its target gene ERK both in mRNA and protein levels, and RDtreatment upregulated miR-423-3p expression and downregulated ERK expression compared with the IR group. Importantly, miR-423-3p mimics inhibited IR increased ERK, CHOP and GRP78 expressions, and enhanced IR decreased Bcl-2expression, and inhibited the IR-induced apoptosis of myocardial cells. The findings of this study suggest that RD treatmentinhibited the endoplasmic reticulum induced apoptosis of myocardial cells via regulating miR-423-3p/ERK signalingpathway in a tree shrew myocardial IR model.