Experimental & Clinical Study On Protective Effects Of Propofol On Hepatic Ischemia Reperfusion Injury

1. BackgroundThe mechanism of hepatic ischemia reperfusion injury(HIRI)is very complicated. At present, the oxygen free radical arouses hepatic cellular membrane, mitochondrial membrane, microsomal membrane and lysosomal membrane lipide peroxideation , which give birth to peroxidation product and their degradeation product-MDA and hydrocarbon .It would aggravate iujury of biological film and breakage stability and integrality of biological film,all those would enhance permeability of biological film and lead to necrose of hepatic cell at the end . Further more oxygen free radical and lipide peroxidation could change and inactivate activity of a great variety of mercapto enzymes, such as Na十-K十ATP (Adenosine Triphosphate) enzyme and SOD etc. On the other hand, at the time of hepatic ischemia ATP would reduce, membrane pump would be dysfunctional and xanthine dehydrogease would change into XOD in the gross. Therefore,the text would be reponsed extent of damage of hepaticl cell by ALT,AST and change of hepatic cellur cytomorphology,reflected peroxidation by MDA and capacity for alleviated free radical by active level of SOD and XOD.Propofol has been reported to have a protective effect against ischemia reperfusion injury in several organs: for example, heart, brain, as well as the lower limbs.The mechanism underlying this protective effect reportedly is involved either radical scavenging or inhibitory effects on calcium channels. In addition, the reported propofol-induced nitric oxide (NO) and vasodilatory prostanoid production might be beneficial during ischemia reperfusion injury. 2. Experimental studyObjective To investigate the protective effect of propofol on hepatic ischemia reperfusion(HIRI) injury and the mechanisms involved.Methods Thirty male SD rats were randomly divided into 5 group of 6 animals each:.groupⅠ:sham operation; groupⅡ: HIRI;0.9%NS was infused at 1ml/kg·h staring from 20min before ischemia until hepatic hilum was clamped.group.Ⅲ: propofol 5mg/kg·h;groupⅣ: propofol 10mg/kg·h;groupⅤ: propofol 20mg/kg·h .HIRI was produced by clamping the hepatic hilum for 30min,then the clamp was removed for 60min reperfusion.Blood samples were taken at the end of 60min reperfusion for determination of ALT,AST activities and meanwhile a hepatic specimen was obtained for determination of MDA content,XOD,SOD and GSH-PX activities and for light and electron microscopic examination.Results Serum ALT and AST activities were significantly higher in groupⅡ,Ⅲ,ⅣandⅤt han that in groupⅠ(P﹤0.01),but were significantly lower in groupⅢ,ⅣandⅤthan in groupⅡ(P﹤0.05,0.01),Serum ALT and AST activities were significantly difference in groupⅢ,ⅣandⅤ(P﹤0.05,0.01).The MDA content,XOD and GSH-PX activity of liver were significantly higher in groupⅡ,Ⅲ,ⅣandⅤt han in groupⅠ,but were significant lower in groupⅡ,Ⅲ,ⅣandⅤt han in groupⅡ(P﹤0.05,0.01). The SOD activity of liver was significant lower in groupⅡthan in groupⅠ, but was significant higher in groupⅢ,ⅣandⅤthan in groupⅠ. The MDA content and XOD activity of liver were significantly higher in groupⅢ,ⅣandⅤthan in groupⅡ, and SOD activity of liver was significant lower in groupⅢ,ⅣandⅤt han in groupⅡ(P﹤0.05,0.01). Whereas the MDA content,XOD and SOD activity of liver were also significantly difference in groupⅢ,ⅣandⅤ(P﹤0.05,0.01).Electron microscopic examination showed that the pathologic changes induced by ischemia-reperfusion were slight in groupⅢ,ⅣandⅤas compared with groupⅡ,and had difference between groupⅢ,ⅣandⅤ.Conclusion propofol could have significant protective effect on the rats liver against ischemia-reperfusion injury,which is related to its antioxidation.3. Clinical studyObjective To investigate the protective effect of propofol on hepatic ischemia reperfusion injury during hepatictomy surgery procedure by observing haemodynamics during operating and liver function of postoperating.Methods Twenty patients,who were ASA gradeⅠ-Ⅱ,scheduled for hepatictomy surgery,were randomly divided into two groups:group A(n = 10)was an untreated control group,group B(n = 10)received propofol 3mg / kg·h which was injected intravenously continously by a micropumb after tratreal intubation. MAP,HR,CVP and SPO2 at times of preoperation(T1),20 minutes after anesthesia(T2),5 and 10 minutes after liver portal vascular occlusion(T3,T4)and 10 and 40minutes after liver portal vascular reopened(T5,T6)were recorded down,liver portal vascular occlusion and patients recovery from anesthesia were recorded,and liver function ALT,AST were measured at times of preoperation postoperation 24h and 72h.Results MAP,HR,CVP and SPO2 have no significant difference between the two groups in every point of time. The times that patients recover from anesthesia had no statistical difference between the two groups.liver function ALT,AST in preoperation have no significant difference between the two groups,but in 24h and 72h of postoperation it has significant difference between the two group(sp<0.05),the levels of ALT and AST were significantly higher than the basic level in every groups. Conclusion The results demonstrate propofol help preventing liver from ischemic and reperfusion damage and don't delay patients recover from anesthesia.