ABSTRACT
Objective To investigate the effect of remifentanil on protein kinase C (PKC) activity during renal ischemia-reperfusion (I/R) in rats.Methods Seventy-five male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 5 groups (n=15 each) using a random number table:sham operation group (group S),I/R group,remifentanil group (group R),naloxone group (group N),and naloxone + remifentanil group (group NR).Renal ischemia was induced by clamping the bilateral renal arteries for 45 min using an atraumatic clamp followed by reperfusion.In R and NR groups,remifentanil 1.0 μg · kg-1 · min-1was infused via the caudal vein starting from 15 min before ischemia until 30 min of reperfusion.In N and NR groups,naloxone 0.3 mg/kg was injected via the caudal vein at 20 min before ischemia and 35 min of ischemia,respectively.The rats were sacrificed at 24 h of reperfusion and the kidneys were removed for determination of the ultrastructure of the renal tubular epithelial cells (using transmission electron microscope),activity of PKC in renal tissues (by ELISA),and expression of the PKC in renal tissues (by immuno-histochemistry).Results Compared with group S,the activity of PKC in renal tissues was significantly increased in the other four groups,and the expression of the PKC in renal tissues was up-regulated in group R.Compared with group I/R,the activity of PKC in renal tissues was significantlyincreased,the expression of PKC in renal tissues was up-regulated,and the pathological changes were attenuated in group R.Compared with group R,the activity of PKC in renal tissues was significantly decreased,the expression of PKC in renal tissues was down-regulated,and the pathological changes were aggravated in N and NR groups.Conclusion The mechanism by which remifentanil attenuates renal I/R injury may be related to up-regulation of PKC expression and increase in PKC activity through activating opioid receptors in rats.
ABSTRACT
Objective To evaluate the effect of remifentanil on Toll-like receptor 2 (TLR2) mRNA expression during renal ischemia-reperfusion (Ⅰ/R) in rats.Methods Fifty-four male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 3 groups (n=18 each) using a random number table:sham operation group (group S),Ⅰ/R group and remifentanil group (group R).Renal Ⅰ/R injury was produced by clamping the bilateral renal arteries for 45 min followed by reperfusion in Ⅰ/R and R groups.Bilateral renal arteries were only exposed but not clamped in group S.Remifentanil 1.0 μg · kg-1 · min-1 was infused via the tail vein starting from 15 min before ischemia until 30 min of reperfusion in group R,while the equal volume of normal saline was given instead in S and Ⅰ/R groups.The animals were sacrificed at 15 min before ischemia and 6 and 24 h of reperfusion,and the renal specimens were obtained for examination of the pathological changes (with light microscope) and for determination of the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) (by ELISA) and expression of TLR2 mRNA (by RT-PCR) and cell apoptosis (by double staining and flow eytometry).The apoptotic rate was calculated.Results Compared with group S,TLR2 mRNA expression was significantly up-regulated,and the contents of TNF-α and IL-6 and apoptotic rate were increased at 6 and 24 h of reperfusion in Ⅰ/R and R groups.Compared with group Ⅰ/R,TLR2 mRNA expression was significantly down-regulated,and the contents of TNF-α and IL-6 and apoptotic rate were decreased at 6 and 24 h of reperfusion in group R.The pathological changes were significantly attenuated in group R as compared with group Ⅰ/R.Conclusion The mechanism by which remifentanil reduces renal Ⅰ/R injury is related to down-regulation of TLR2 expression and decrease in TLR2 activity and inhibition of inflammatory responses in renal tissues and cell apoptosis in rats.