Objective To investigate the role of opioid receptors in remifentanil-induced attenuation of renal ischemia/reperfusion (I/R) injury in rats.Methods Seventy-five male Sprague-Dawley rats weighing 250-300 g were randomly divided into 5 groups ( n =15 each):sham operation group (group S),group I/R,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 groups R and NR,remifentanil was infused at 1.0 μg· kg-1 · min-1 via the caudal vein starting from 15 min before ischemia until 30 min of reperfusion,while groups S,I/R and N received the equal volume of normal saline instead of remifentanil.In groups N and NR,naloxone 0.3 mg/kg was injected via the caudal vein at 20 min before ischemia and at 35 min after ischemia respectively,while groups S,I/R and R received the equal volume of normal saline instead of naloxone.Blood and urine samples were collected from the femoral vein and urinary bladder respectively at 24 h of reperfusion for determination of the levels of serum creatinine (Cr) and blood urea nitrogen (BUN),urinary N-acetyl-β-D-glucosaminidase (NAG) and γ-glutamyl transpeptidase (γ-GT).The rats were sacrificed at 24 h of reperfusion and the renal tissues were removed for determination of nalondialdehyde (MDA) content and superoxide dismutase (SOD) activity.Pathological changes in renal tissues were observed with light microscope.Results Compared withgroup S,the levels of serum Cr and BUN,urinary NAG and γ-GT,and MDA were significantly increased,while the activity of SOD was significantly decreased in the other 4 groups ( P ＜ 0.05 or 0.01 ) and pathological changes in renal tissues were observed in the other 4 groups.Compared with group I/R,the levels of serum Cr and BUN,urinary NAG and γ-GT levels,and MDA were significantly decreased,while the activity of SOD was significantly increased ( P ＜ 0.01 ),and the pathological changes were reduced in group R,and no significant change was found in the parameters mentioned above in groups N and NR ( P ＞ 0.05).The pathological changes were similar in groups I/R,N and NR.Compured with group R,serum Cr and BUN concentrations,urinary NAG and γ-GT levels and MDA concent were increased,while SOD activity were decreased ( P ＜ 0.05 or 0.01 ).Conclusion Opioid receptors mediate remifentanil-induced attenuation of renal I/R injury in rats.

Objective To investigate the effects of different doses of remifentanil on the renal ischemiareperfusion (I/R) injury in rats. Methods Sixty male SD rats weighing 220-250 g were randomly divided into 5 groups ( n = 12 each): sham operation group (group S), model group (group M), low, median and high doses of remifentanil groups (RL, RM and RH groups). The rats were anesthetized with intraperitoneal 5% chloral hydrate 6 ml/kg. Renal ischemia was induced by clamping the bilateral renal arteries for 45 min using an atraumatwere infused via the caudal vein 15 min before ischemia respectively and the infusion was stopped at 30 min of reperfusion, while S and M groups received equal volume of normal saline instead. Blood samples were collected from the femoral vein at 30 min and 24 h of reperfusion for measurement of serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations. The rats were sacrificed at 24 h of reperfusion and the renal tissues were removed for determination of MDA content, SOD and Ca2+ -ATPase activities. Pathological changes in renal tissues were observed with light and electron microscopes. Results Compared with group S, the concentrations of serum Cr and BUN and content of MDA were significantly increased, while activities of SOD and Ca2+ -ATPase were significantly decreased in the other 4 groups ( P ＜ 0.05 or 0.01). Compared with group M, the concentrations of serum Cr and BUN and content of MDA were significantly decreased, activities of SOD and Ca2+ -ATPase were significantly increased (P ＜0.05 or 0.01) and the pathological changes were reduced in RH, RM and RL groups. The plasma BUN and Cr concentrations and MDA content were decreased gradually and SOD and Ca2+ -ATPase activities were increased gradually with the increase in the doses of remifentanil in RL, RM and RH groups ( P ＜ 0.05 or 0.01 ).Remifentanil infusion significantly attenuated the pathologic changes in a dose-dependent manner. Conclusion Remifentanil can reduce the renal I/R injury in a dose-dependent manner by inhibiting lipid peroxidation and increasing Ca2+ -ATPase activity.

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.

Objective To investigate the effect of remifentanil on nucleotide-binding oligomerization domain 1 (NOD1) mRNA expression in rats with renal ischemia-reperfusion (I/R) injury.Methods Sixty male Sprague-Dawley rats,weighing 220-250 g,were randomly divided into 3 groups (n =20 each):sham operation group (S group),I/R group and remifentanil group (R group).Renal ischemia was induced by occlusion of bilateral renal arteries for 45 min followed by 24 h reperfusion in groups I/R and R.Remifentanil 1.0 μg· kg-1 · min-1 was infused until 30 min of reperfusion starting from 15 min before ischemia 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 at 3,6,24 h of reperfusion and the kidneys were removed for microscopic examination and polymorphonuclear leukocyte (PMN) count and for measurement of NOD1 mRNA expression (by RT-PCR).The apoptotic rate was determined by flow cytometry double staining method.Results Compared with group S,NOD1 mRNA expression was up-regulated,and the apoptotic rate and PMN count were significantly increased at each time point during reperfusion in group I/R,and the apoptotic rate and PMN count were significantly increased at each time point during reperfusion,and NOD1 mRNA expression was up-regulated at 6 and 24 h of reperfusion in group R (P ＜ 0.01).Compared with I/R group,NOD1 mRNA expression was down-regulated,and the apoptotic rate and PMN count were significantly decreased at each time point during reperfusion (P ＜ 0.05 or 0.01),and the pathological changes were significantly attenuated in group R.Conclusion Remifentanil can reduce the renal I/R injury by down-regulating the expression of NOD1 mRNA and inhibiting inflammatory response and apoptosis.

Objective To evaluate the effect of remifentanil on cell apoptosis during renal ischemia-reperfusion (I/R) in rats.Methods Seventy-five male Sprague-Dawley rats,weighing 220-250 g,were randomly divided into 3 groups (n =25 each):sham operation group (group S),I/R group,and remifentanil group (group R).Renal ischemia was induced by occlusion of the bilateral renal arteries for 45 min followed by reperfusion in groups I/R and R.Remifentanil was infused at 1.0 μg· kg-1 · min-1 via the caudal 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 of remifentanil in groups S and I/R.At 15 min before ischemia (T0) and 3,6,12,24 h of reperfusion (T1-4),5rats were anesthetized and sacrificed,and renal specimens were obtained to detect the apoptotic rate and expression of Bax and Bcl-2 protein (by flow cytometry) and mRNA (by RT-PCR).The ratios between Bcl-2/Bax protein and mRNA expression were calculated.The pathological changes of renal tubules were scored.Results Compared with group S,the pathological scores and apoptotic rate were significantly increased at T1-4,and ratios between Bcl-2/Bax protein and mRNA expression were increased at T1,2,while decreased at T3,4 in groups R and I/R (P ＜0.01).Compared with group I/R,the pathological scores and apoptotic rate were significantly decreased at T1-4,while the ratios between Bcl-2/Bax protein and mRNA expression were increased in group R (P ＜ 0.05 or 0.01).Compared with the baseline value at T0,the pathological scores and apoptotic rates were significantly increased at T1 4,and the ratios of Bcl-2/Bax protein and mRNA expression were increased at T1,2,while decreased at T3,4 in groups R and I/R (P ＜ 0.01).Conclusion Regulation of Bcl-2/Bax expression and inhibition of cell apoptosis in renal tissues are involved in the mechanism by which remifentanil reduces renal I/R injury in rats.

Objective To evaluate the effect of dexmedetomidine pretreatment on expression of se-cretion protein of Clara cell secretory protein(CC16)during endotoxin-induced acute lung injury(ALI) in rats.Methods One hundred and twelve healthy Wistar rats of both sexes, aged 8-12 weeks, weighing 250-350 g, were divided into ALI group(n=56)and dexmedetomidine pretreatment group(group DEX, n= 56)using a random number table.ALI was induced by intravenously injecting lipopolysaccharide (LPS)5 mg∕kg over 1 min.Dexmedetomidine 10 μg∕kg was intravenously infused over 10 min starting from 10 min before LPS in group DEX.At 10 min before LPS injection and 0.5, 1, 2, 4, 6 and 24 h after LPS injection, 8 rats were sacrificed and lungs were removed for examination of the pathological changes(with a light microscope)and ultrastructure of Clara cells(with a transmission electron microscope)and for deter-mination of CC16 expression in bronchioles(by immunohistochemistry). Results Compared with the baseline at 10 min before LPS injection, the expression of CC16 in bronchioles was significantly down-regu-lated at 1, 2, 4, 6 and 24 h after LPS injection in group ALI and at 1, 2, 4 and 6 h after LPS injection in group DEX(P<0.01), the pulmonary small arterial hyperemia, alveolar septa edema, red blood cell exudation and inflammatory cell infiltration were found, the Clara cells in bronchioles were reduced, the secretory granules in the cytoplasm were reduced, and the mitochondria were swollen and deformed after in-jection of LPS.Compared with group ALI, the expression of CC16 in bronchioles was significantly up-regu-lated at 1, 2, 4, 6 and 24 h after LPS injection(P<0.01), the pathologic changes of lung tissues were significantly attenuated, and the number of Clara cells was increased in group DEX.Conclusion The mechanism by which dexmedetomidine pretreatment reduces endotoxin-induced ALI may be related to up-regulating CC16 expression in rats.