OBJECTIVE: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.Free PDF Download
To cite this article
W.-Y. Zhang, Q.-L. Zhang, M.-J. Xu
Effects of propofol on myocardial ischemia reperfusion injury through inhibiting the JAK/STAT pathway
Eur Rev Med Pharmacol Sci
Vol. 23 - N. 14