Objective: The purpose of this study was to explore the influence of Ghrelin on myocardial injury of septic rats through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway.
Materials and methods: A total of 36 Sprague-Dawley rats were randomly divided into normal group (n=12), model group (n=12), and Ghrelin group (n=12). The rats in the normal group were fed normally, while those in the model group were intraperitoneally injected with endotoxin to establish the sepsis model. The rats in the Ghrelin group were given intraperitoneal injection of Ghrelin solution to prepare the sepsis model. 9 h later, the specimens were obtained. Then, the expressions of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were detected via immunohistochemistry, and the protein expressions of phosphorylated JAK (p-JAK) and STAT3 were determined by Western blotting (WB). Next, enzyme-linked immunosorbent assay (ELISA) was performed to measure the content of IL-6 and TNF-α, and quantitative Polymerase Chain Reaction (qPCR) was applied to examine the messenger ribonucleic acid (mRNA) expressions of JAK and STAT3. Finally, the cell apoptosis was detected through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.
Results: The results of immunohistochemistry showed that compared with those in the normal group, the positive expression levels of IL-6 and TNF-α were markedly increased in other groups (p<0.05), while in comparison with those in the model group, the positive expression levels of IL-6 and TNF-α were decreased significantly in the Ghrelin group (p<0.05). The WB results indicated that the model group and Ghrelin group had remarkably higher protein expression levels of p-JAK and STAT3 than the normal group (p<0.05), and Ghrelin group exhibited notably lower protein expression levels of p-JAK and STAT3 than the model group (p<0.05). According to the results of qPCR, the relative mRNA expression levels of JAK and STAT3 were distinctly raised in the model group and Ghrelin group in comparison with those in the normal group (p<0.05), while they were reduced evidently in the Ghrelin group compared with those in the model group (p<0.05). Furthermore, it was manifested in the results of ELISA that the model group and Ghrelin group had prominently elevated content of TNF-α and IL-6 compared with normal group (p<0.05), and Ghrelin group displayed significantly lowered content of TNF-α and IL-6 in comparison with the model group (p<0.05). Moreover, the TUNEL results revealed that the apoptosis rate was remarkably higher in the other two groups than that in the normal group (p<0.05), while it was evidently lower in the Ghrelin group than that in the model group (p<0.05).
Conclusions: Ghrelin can inhibit inflammatory response and apoptosis in the process of myocardial injury in septic rats by repressing the JAK/STAT signaling pathway.