Objective To investigate the protection mechanism of propofol for rat model of myocardial ischemia reperfusion injury (MIRI).
Methods Totally 60 rats were randomly divided into sham operation group (group A), sham operation plus propofol group (group B), myocardial ischemia reperfusion group (group C), myocardial ischemia reperfusion plus propofol group (group D). In the group A, the left anterior descending coronary artery and the great cardiac vein were not clipped after threading at 2 mm of the root of the left auricle, and sutured after 60 minutes. In the group B, 6 mg/kg propofol was pumped intravenously from the beginning of operation to 60 minutes after operation. Myocardial ischemia reperfusion model was established in the group C. In the group D, 6 mg/kg propofol was pumped intravenously from the beginning of modeling to 60 minutes after operation. HE staining was used to observe the histopathological changes of myocardium of the rats. TUNEL assay was used to detect apoptosis rate. RT-PCR assay was used to detect expressions of mRNA of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Western Blot assay was used to detect protein expressions of high mobility group box 1 (HMGB1) and Toll-like receptor 4 (TLR4).
Results There was no significant abnormity in myocardial microstructure in the group A and B. However, myocardial microstructure injury was significant in the group C, and the degree of injury in the group D was milder than that in the group C. The myocardial apoptosis index was (0.39±0.05)% in the group C, which was significantly higher than (0.01±0.02)% in the group A, (0.01±0.03)% in the group B and (0.17±0.03)% in the group C (t=15.36, 15.44, 9.73, P < 0.01). The mRNA expression levels of TNF-α and IL-6 in the groups C and D were significantly higher than those in the group A (t=16.26, 8.04, 17.66, 11.83, P=0.01, 0.02, 0.01, 0.01), and the mRNA expression levels of TNF-α and IL-6 in the group D were significantly lower than those in the group C (t=9.04, 8.55, P=0.03, 0.04). The protein expression levels of TLR4 and HMGB1 in the group C and D were significantly higher than those in the group A (t=15.87, 9.11, 11.95, 8.73, P < 0.01), and the protein expression levels of TLR4 and HMGB1 in the group D were significantly lower than those in the group C (t=10.02, 9.83, P=0.03, 0.03).
Conclusion Propofol can reduce myocardial injury and inflammation induced by MIRI in rats, and its mechanism may be related to down regulation of TLR4 and HMGB1 in myocardial tissues.
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