Abstract
BackgroundExtensive experimental and clinical studies have shown that ischemic preconditioning (IP) can produce protective effects during hepatic ischemia reperfusion (I/R) injury. Our recent studies indicate that rat liver I/R injury is related to an abnormal increase in leukotriene (LT) C4 production. However, the mechanisms underlying IP actions on LTC4 generation during hepatic I/R injury remain to be explored. MethodsWe randomly divided adult male Sprague-Dawley rats into sham (control), I/R, and IP groups (n = 6). We subjected rat liver to 60 min partial hepatic ischemia followed by 5 h reperfusion with saline administered intravenously. We detected protein expression of LTC4 synthase (LTC4S) with Western blot, and measured LTC4 synthesis enzymes' activities and content by reverse-phase high-performance liquid chromatography. We assessed tissue injury using serum aspartate aminotransferase and aspartate aminotransferase activities and histologic changes. We examined liver tissue glutathione levels by a biochemical method. ResultsIschemic preconditioning markedly decreased LTC4 content, reduced LTC4S protein expressions, and inhibited LTC4 synthesis enzymes' activities in rat liver compared with the I/R group (P < 0.05). We also observed a decline in serum alanine aminotransferase and aspartate aminotransferase activities (P < 0.05), together with hepatic tissue glutathione elevation (P < 0.05) in the IP groups. Positive expression of LTC4S on hepatocytes and sinusoidal endothelial cells in the IP group was significantly lower than that in the I/R group. ConclusionsThese findings demonstrate that reduced LTC4 production by IP treatment during hepatic I/R injury could partially result from the down-regulation of LTC4S protein expression and the depression of LTC4 synthesis enzyme activity. They suggest that the beneficial effects of IP may be involved in repression of LTC4 generation during hepatic I/R injury.
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