Effect of propofol pretreatment on dephosphorylation of Drp1 Ser637 during kidney injury induced by hepatic ischemia-reperfusion in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of propofol pretreatment on dephosphorylation of phospho-dynamin-related protein 1 (p-Drp1) Ser637 during kidney injury induced by hepatic ischemia-reperfusion (I/R) in mice.Methods Thirty healthy SPF male C57 mice,weighing 20-25 g,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (group S),hepatic I/R group (group HI/R) and propofol pretreatment group (group P).Hepatic I/R was produced by occluding the blood supply to the left lateral and median lobes of liver for 60 min followed by reperfusion in anesthetized mice.In group P,1％ propofol 30 mg/kg was intraperitoneally injected at 30 min before operation,while the equal volume of normal saline was given instead in S and HI/R groups.Blood samples were collected from the left ventricle at 6 h of reperfusion for determination of the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr).Renal tissues were obtained for determination of cell apoptosis (by TUNEL) and expression of Drp1,p-Drp1 Ser637,cytochrome c (Cyt c) and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of mitochondria (by transmission electron microscopy).Apoptosis index was calculated.Results Compared with group S,the serum BUN and Cr concentrations and apoptosis index were significantly increased,the expression of p-Drp1 Ser637 was down-regulated,and the expression of Cyt c and cleaved caspase-3 was up-regulated (P＜0.05),and microscopic examination showed that mitochondria was swollen with vacuolization and mitochondrial cristae was irregularly distributed or disrupted and shortened in HI/R and P groups.Compared with group HI/R,serum BUN and Cr concentrations and apoptosis index were significantly decreased,the expression of p-Drp1 Ser637 was up-regulated,the expression of Cyt c and cleaved caspase-3 was down-regulated (P＜0.05),and the ultrastructure of mitochondria was markedly improved in group P.There was no significant difference in the expression of Drp1 in renal issues between the three groups (P＞0.05).Conclusion The mechanism by which propofol pretreatment mitigates hepatic I/R-induced kidney injury is related to inhibiting dephosphorylation of Drpl Ser637 in mice.