Butorphanol protects on myocardial ischemia/reperfusion injury in rats through MAPK signaling pathway.

Abstract

To explore the influence of butorphanol on myocardial ischemia/reperfusion (I/R) injury in rats through the mitogen-activated protein kinase (MAPK) signaling pathway. The I/R model in Sprague-Dawley rats was established. The rats were randomly divided into normal group (n=20), myocardial I/R model group (model group, n=20), and butorphanol treatment group (treatment group, n=20). Next, the liver function indicators such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), and the myocardial function index creatine kinase (CK) in rats were detected. ELISA was carried out to measure the relative levels of tumor necrosis factor-gamma (TNF-γ), interleukin-6 (IL-6), and IL-1α in serum samples of rats. The cardiac function indexes were examined via magnetic resonance imaging (MRI) and echocardiography (ECG). Besides, the pathological changes of the myocardial tissues were detected through hematoxylin-eosin (HE) staining. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting were performed to measure the mRNA and protein expression levels of the relative genes in the MAPK signaling pathway in the rat myocardial tissues. The serum levels of ALP, ALT, and CK in I/R model group were significantly higher than those in the normal group. In I/R model group, the relative levels of TNF-γ, IL-6, and IL-1α, as well as left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd), were remarkably higher, while the fractional shortening (FS, %) and the ejection fraction (EF, %) were lower in comparison with those in the normal group. The HE staining results showed that the myocardial tissues in the I/R model group exhibited severe injury. The expression levels of Caspase3, MAPK, and c-Jun N-terminal kinase (JNK) were clearly higher in the I/R model group than those in the treatment group (p<0.05), while the expression level of extracellular regulated protein kinase 1 (ERK1) was remarkably lower (p<0.05). The protein level of MAPK in the treatment group was overtly reduced compared with that in the I/R model group (p<0.05). Butorphanol can modulate the recovery of the myocardial injury in the rats after the myocardial I/R by inhibiting the MAPK signaling pathway.