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Background:The liver ischemia-reperfusion injury is inevitable pathophysiological phenomen-on in the liver and gallbladder surgery. When Shock, because of serious abdominal infection, bleeding and other reasons, has been the recovery; When the liver is cut partly because of liver tumor; When liver is damaged seriously, or is transplanted; The liver ischemia-reperfusion injury can not be ignored problem. To elaborate the mechanism of hepatic ischemia-reperfusion injury and investigate some effective methods or drug treatments, which has been a hot and difficult for many scholars and clinicians all the time. At present studies suggest that the main mechanisms of hepatic ischemia-reperfusion injury are:oxygen free radical damage, calcium overload and cell factor damage. Ulinastatin and verapamil are represent durgs aimed at these mechanisms. Two drugs used alone can play a protective role in the hepatic ischemia-reperfusion injury, however, the effect of combination therapy has not been clearly reported.Objective:The purpose of this topic is studying protective effect of ulinastatin combined with verapamil on liver ischemic-reperfusion injury in rats. Approaching ulinastatin and verapamil possible mechanism in ischemia-reperfusion injury, the purpose is to guide the ulinastatin comb-ined with verapamil at clinical application.Methods:Liver I/R model in vivo rats were established. Healthy male wistar rats (n=40) were randomly divided into five groups (n=8):sham-operation group (Group A), ischemia-reperfusion group (Group B), pretreatment with ulinastatin group (Group C), pretreatment with verapamil group (Group D),and pretreatment with ulinastatin combined with verapamil group (Group E). Group A:The abdomen was opened and then closed; Group B:Hepatic inflow was occluded for 30 minutes by pringlep’s maneuver, and then abdomen was closed; Group C:Ulinastatin was administered intraperitoneally 30 minutes before the experiment, the dealing was the same as group B; Group D:Intravenous verapamil was given 10 minutes before the experiment, the dealing was the same as group B; Group E:The methods was the same as group B, group C and group D. The concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in serum were measured, and the histopathological changes of liver were also observed.Result:1. The concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH):Compared with sham-operated group rats, the concentrat-ions of ALT, AST, LDH of ischemia-reperfusion group was significantly increased, the difference has statistics significance (P<0.01); Compared with ischemia-reperfusion group rats, the concentrations of ALT, AST, LDH of pretreatment with ulinastatin group, pretreatment with verapamil group and pretreatment with ulinastatin combined with verapamil group were significantly reduced, the difference has statistics significance (P<0.01); Compared with pretreatment with ulinastatin combined with verapamil group rats, the concentrations of ALT, AST, LDH of pretreatment with ulinastatin group, pretreatment with verapamil group was significantly increased, the difference has statistics significance (P<0.05); Compared with pretreatment with ulinastatin group rats, the concentrations of ALT, AST, LDH of pretreatment with verapamil group was not significantly different (P>0.05).2. The concentrations of tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1(3):Compared with sham-operated group rats, the concentrations of TNF-α, IL-1βof ischemia-reperfusion group was significantly increased, the difference has statistics significance (P<0.01); Compared with ischemia-reperfusion group rats, the concentrations of TNF-α, IL-1βof pretreatment with ulinastatin group, pretreatment with verapamil group and pretreatment with ulinastatin combined with verapamil group were significantly reduced, the difference has statistics significance (P<0.01); Compared with pretrea-tment with ulinastatin combined with verapamil group rats, the concentrations of TNF-a, IL-1βof pretreatment with ulinastatin group, pretreatment with verapamil group was significant-1y increased, the difference has statistics significance (P<0.05); Compared with pretreatment with ulinastatin group rats, the concentrations of TNF-a, IL-1βof pretreatment with verapamil group was not significantly different (P>0.05).3. the histopathological change of liver in group B was the severest, The change of group C and D were better than group B, The change of group E was the slightest.Conclusion:1. Compared with the sham-operated group, the level of TNF-α, IL-1βin ischemia-reperfusion group was significantly increased, further confirming that the increased level of TNF-α, IL-1βis closely linked to liver ischemic-reperfusion injury.2. Compared with ischemia-reperfusion group, both ulinastatin and verapami can reduce liver ischemia-reperfusion injury and protect the liver cells. Ulinastatin combined with verapamil has a better effect than ulinastatin or verapami.
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