The Lung Injury Induced By The Total Hepatic Ischemia-reperfusion In Rats And Its Protection

Background and Objective:The total hepatic ischemia-reperfusion is unavoidable in liver operation and liver transplantation, after operation, lots of inflammatory mediator, oxygen redicals, pour into the lung, and may lead to acute lung injury or respiratory failure. whose function affect patients' survival rate after operation.We have established the model of total hepatic ischemia-repersusion bysurgery to observe changes of the vulnerantcy tokines and AQP1, the energymetabolism of mit-ochondriathe, and the regulation of H2S/CSE, CaN signaltransduction path, we also use NaHS, FK-506, Spiron, MP to search the lung injury and protection.Our experiment is divided into two parts. Firstly, we explore the possible mechansim of the lung injury after total hepatic ischemia-repersusion. Secondly, we are to ascertain the energy metabolism of mitochondria on the lung injury after total hepatic ischemia-repersusion.Method:We had established the model of total hepatic ischemia-repersusion by surgery.First part, one hundred eighty-four Wistar rats were divided into twenty-three groups, and eight rats in each group:control; ischemia-repersusion 20min:Oh,2h, 6h,12h,24h,48h,72h; ischemia-repersusion 40min:Oh,6h,72h; FK506, Spiron, MP, NaHS control and 20min+6h interventian algroup; Spiron, MP 40min+6h and 40min+72h interventianal group. Second part, ninety Wistar rats were divided into twelve groups, eight rats in each group:control; ischemia 20min; FK506,Spiron, MP, NaHS control and 20min+6h interventianal group.The H2S, MDA, AngⅡ, ALD, TNF-a, IL-8 in blood, and the activity of CSE,the content of ICAM-1, NF-κB, CaN, AQP1, IL-8 in lung tissue are determinded. Light and electron microscope was used to observe the pathological change of the lung. Also, we determined the respiratory control rate(RCR), P/O ratio, membrane potential and the activity of mitochondria enzyme to research the mechanism of the lung injury after ischemia-reperfusion. Result:The results of the first part were as follows:Compared to the control group, in the ischemia 20min group, the level of TNF-a, H2S, MDA, AngⅡin blood, IL-8 in blood and lung, W/D, ICAM-1,NF-κB in lung were significantly increased after ischemia-reperfusion, and reached the peak at about 2-12h. The AQP1 began to decrease with the minimus at 6h after the ischemia-reperfusion. The level of ALD in plasma and lung, the content, activity and mRNA of CaN in lung reached the peak twice at 2h and 6-12h, and decreased after reperfusion. Most of these observing indexes got to nomal level at 72h after the operation. Pathological examination indicated that the most serious injure occur at 6h after ischemia-reperfusion. The trend in the ischemia 40min was the same, but the indexes changed more obviously than the ischemia 20min group, and the pathological examination showed the tissue injury was more severity. After the intervention of the four medicines:FK506, MP, Spiron, NaHS, the injury of the lung tissue were improved under the varying degrees.The results of the second part were as follows:After total hepatic ischemia reperfusion, the activity of the mitochondria enzyme changes, and the RCR,P/O and membrane potential were significantly lower. After the intervention of the four medicines above, the respiratory function and ATPase activity were improved under the varying degrees.Conclution:The total hepatic ischemia-reperfusion may induce the injury of the lung, and the most serious time is at the 6 hours after ischemia-reperfusion. The mechanism may be involved in the activating of vulnerant cytokines, down-regulation of AQP1, changes of energy metabolism of mitochondriathe. The regulation of endogenous H2S/CSE system, up-regulation of CaN may play an important role in lung injury. MP, FK-506,Spiron, NaHS may protect lung injury after ischemia-reperfusion.