Effects Of Ulinastatin Combined With Magnesium Sulfate Pretreatment On Hepatic Ischemia-reperfusion Injury

Objective:To study the protective effect of ulinastatin combined with magnesium sulfate pretreatment on hepatic ischemia-reperfusion injury in patients undergoing partial hepatectomy and to explore the possible mechanism of its protective effect.Methods:One hundred patients with partial hepatectomy under general anesthesia were selected and divided randomly into Control group,ulinastatin group,magnesium sulfate group,ulinastatin and magnesium sulfate combination group,with 25 patients in each group.Ulinastatin group,ulinastatin（10000 U/kg in 100 ml saline）was dripped into the internal jugular vein with 100 ml/h before skin incision.magnesium sulfate group,magnesium sulfate（30mg/kg in 100 ml saline）was dripped into the internal jugular vein with 100 ml/h before skin incision,and then pumped into the internal jugular vein with 15mg/kg/h continuously until the end of the operation.Combined group,the same with ulinastatin group and magnesium sulfate group;Control group,as carried out the normal operation process,without any drug treatment.The blood samples（5 ml）were collected from the internal jugular vein of four groups patients in preoperative anesthesia,after operation,post-operation Day1,post-operation Day3,post-operation Day5 respectively.These blood samples were used to detect liver function（ALT,AST）index,serum MDA and SOD level.Results:1.There were no statistically significant differences among the four groups in age,weight,number of hepatic portal occlusion,blocking time,intraoperative blood loss and length of stay（P>0.05）.2.Comparison within the group:（1）HR:Control group,HR at T₁ and T₂ were significantly higher than that at T₀,with statistically significant differences（P=0.031,0.031）.There was no significant change in HR at different time points in other groups（P>0.05）.（2）MAP:the MAP comparison at different time points in the four groups showed no significant change（P>0.05）.Comparison among groups:there was no statistical difference in HR and MAP between the four groups（P>0.05）.There was no statistical difference in the level of HR and MAP among the four groups at each time point during the operation（P>0.05）.3.Serum ALT level:（1）compare within groups:compared with the preoperative level,the serum ALT level of patients in the Control group and the UTI group was significantly increased on the first day after surgery（P=0.031,0.014）,and then gradually decreased towards the preoperative level.There was no significant difference in the remaining groups（P>,0.05）.（2）comparison between groups:compared with the Control group,the serum ALT level of patients in the UTI+MgSO4 group was significantly reduced on the 5th day after surgery（P=0.047）,while there was no significant difference in the expression of serum ALT level between the groups before surgery,after surgery,on the 1st day after surgery and on the 3rd day after surgery（P>0.05）.4.Serum AST level:（1）compare within groups:compared with the preoperative results,serum AST level of patients in the Control group,MgSO4 group and UTI+MgSO4 group were significantly increased on the first day after surgery,with statistically significant differences（P=0.0001,0.0003,0.005）.Subsequently,serum AST levels in the three groups on day 3 and day 5 were significantly lower than that on day 1,with statistically significant differences（P<0.05）.（2）Comparison among groups:compared with the Control group,the serum AST levels of the UTI group,the MgSO4 group and the UTI+MgSO4 group had significantly smaller increases on the first day after surgery（P=0.003,0.018,0.019）.On the 5th day after the operation,the serum AST level of UTI group,MgSO4 group and UTI+MgSO4 group decreased significantly（P<0.001）,and the serum AST level of UTI+MgSO4 group decreased more significantly than that of UTI group and MgSO4 group（P=0.003,0.048）.5.Serum SOD level:（1）compare within groups:compared with the preoperative results,the serum SOD level in all four groups increased significantly after the operation,and then gradually decreased on the first day,the third day and the fifth day after the operation,and the changes in all four groups were statistically significant（P=0.000,0.002,0.017,0.002）.（2）comparison among groups:compared with the Control group,the serum SOD level of UTI group,MgSO4 group and UTI+MgSO4 group all increased significantly at the end of the operation（P<0.001）,and the difference was more significant in UTI+MgSO4 group than in UTI group and MgSO4 group（P<0.001）.Subsequently,the serum SOD level of the UTI+MgSO4group was higher than that of the other three groups on the 1st and 3rd day after the operation,and the difference was statistically significant（P<0.001）.6.Serum MDA level:（1）compare within groups:serum MDA level in all four7.groups increased at the end of surgery compared with that before surgery,and the changes in the Control group were statistically significant（P=0.015）.Subsequently,the serum MDA level of each group decreased gradually after the operation,and there was no significant statistical difference in the group.（2）comparison between groups:compared with the Control group,the increase of serum MDA level in UTI group, MgSO4 group and UTI+MgSO4 group was significantly smaller at the end of the operation（P=0.009,0.016,0.001）.On the first day after the operation,the serum MDA level of the UTI+MgSO4 group was significantly lower than that of the Control group,the UTI group and the MgSO4 group,and the difference was statistically significant（P=0.001,0.002,0.012）.8.Compared with the Control group,the length of stay in the UTI+MgSO4group was significantly shorter,and the difference was statistically significant（P=0.001）.Conclusion:Ulinastatin combined with magnesium sulfate pretreatment can reduce hepatic ischemia reperfusion injury,and the effect is more significant than that of administration alone.