Remifentanil reduces renal ischemia/reperfusion injury in rats via mediating Fas apoptosis signal pathway

Objective To investigate the effects and mechanism of remifentanil on renal ischemia/reperfusion(IR) injury via mediating Fas apoptosis signal pathway in rats. Methods Sprague-Dawley rats were divided into 3 groups (n=20 each) by using the random number table method: sham operation group (S group), IR control group (IR group), experimental group (R group). The renal IR model was prepared by clamping the bilateral renal arteries for 45 min followed by reperfusion in IR group and R group. In R group, remifentanil was infused at 1.0 μg·kg-1·min-1 via the tail vein starting from 15 min before ischemia until 30 min of reperfusion. In S group and IR group, the same volume of physiological saline was given. At 15 min before ischemia and at 3 h, 12 h, 24 h of reperfusion, the renal tissue samples were obtained for detecting the apoptosis rate by flow cytometry, determining the level of Fas mRNA expression by RT-PCR, the level of caspase-8 and caspase-3 activation by Western blotting, and scoring the number of kidney tubules injury by Paller’ method. Results In IR group, the renal tubular injury score, the apoptosis rate, the expression of Fas mRNA and the activation of caspase-3 in renal tissue increased at 3 h after reperfusion, and those continued to increase at 12 h after reperfusion and reached the peak at 24 h after reperfusion (P<0.01), and the activity of caspase-8 increased at 3 h, reached the peak at 12 h after reperfusion and decreased at 24 h after reperfusion (P<0.01). As compared with S group, the renal tubular injury score, apoptosis rate, the expression of Fas mRNA and the activation of caspase-3 at 3 h, 12 h and 24 h of reperfusion and the activation of caspase-8 at 12 h, 24 h of reperfusion were all increased in IR group and R group (P<0.05 or 0.01). As compared with IR group, the renal tubular injury score, apoptosis rate, the expression of Fas mRNA and the activation of caspase-8 and caspase-3 at 3 h, 12 h and 24 h of reperfusion were decreased in R group (P<0.05 or 0.01). Conclusion Remifentanil inhibits cell apoptosis and alleviates renal IR damage by reducing the expression of Fas receptor and the activation of caspase-8 and caspase-3, and regulating the apoptotic signal pathway of Fas. Key words: Rats; Kidney; Reperfusion injury; Piperidines; Apoptosis