Effects of propofol on myocardial ischemia reperfusion injury through inhibiting the JAK/STAT pathway.

Abstract

The aim of this study was to investigate the effect of propofol (PPF) on myocardial ischemia-reperfusion injury (MIRI) by inhibiting the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, and to explore the possible underlying mechanism. A total of 60 Sprague-Dawley (SD) rats were randomly divided into 5 groups, including the Sham group (n=12), the MIRI model group (n=12), the PPF pretreatment group (n=12), the RG81640-CH (RG) pretreatment group (n=12) and the PPF+RG pretreatment group (n=12). The hemodynamic parameters of rats in each group were measured. Serum samples were collected from rats in each group. Meanwhile, the levels of lactate dehydrogenase (LDH), creatine kinase-muscle/brain (CK-MB), nicotinamide adenine dinucleotide+ (NAD+) and inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein (MCP), were detected by enzyme-linked immunosorbent assay (ELISA). Myocardial infarction area of rats in each group was detected via 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Moreover, the JAK/STAT pathway, as well as apoptosis indexes in myocardial cells of rats, were detected via Western blotting. Compared with the Sham group, the contents of LDH, CK-MB, NAD+ and inflammatory factors, as well as the area of myocardial infarction were significantly increased in the MIRI group (p<0.05). In terms of hemodynamic parameters, the left ventricular end-diastolic pressure (LVEDP) was significantly increased in the MIRI group. However, heart rate (HR), left ventricular developed pressure (LVDP) and maximal rate of the increase/decrease of left ventricular pressure (±dp/dtmax) were significantly decreased in the MIRI group when compared with those of the Sham group (p<0.05). Compared with the MIRI group, the contents of LDH, CK-MB, NAD+ and inflammatory factors, as well as the area of myocardial infarction and LVEDP were significantly declined in the PPF group. Meanwhile, HR, LVDP and ±dp/dtmax were remarkably increased (p<0.05). No significant differences in each index were found between the PPF + RG group and the MIRI group (p>0.05). Western blotting revealed that the protein level of B-cell lymphoma-2 (Bcl-2) was remarkably increased, while the activity of Caspase-3 was decreased in the PPF group when compared with the MIRI group (p<0.05). In addition, the protein expression levels of JAK1, STAT1 and STAT3 in the PPF group were significantly decreased than those of the MIRI group (p<0.05). However, completely opposite trends were found in the RG group. PPF reduces the release of inflammatory factors and alleviates tissue damage caused by myocardial apoptosis in MIRI rats by inhibiting the activation of the JAK/STAT pathway. Our findings indicate that PPF has a certain myocardial protective effect on MIRI.