| Background and Objective:Liver transplantation and most liver resection are clinically normal.The total hepatic ischemia-reperfusion injury is a common pathophysiological processes in liver operation, which not only affects the function of the liver itself, but also damage the distant organs-intestine. We have established the model of total hepatic ischemia-repersusion by surgery to dynamically detect the changes of H2S, TNF-α, ALD, AngⅡ, MDA in blood plasma, the activity of CSE and the content of ALD, NF-kB in intestine. We aslo detect the changes of the intestinal tissue CaN Aβgene expression using RT-PCR and observe the pathological damage of mucous membrane of small intestine with light microscope and the pattern and structure changes of the small intestine with electron microscope.Secondly, we design to use the NaHS, MP, spironolactone and FK506 to interfere in the process of intestinal injuries, observing the same index as above. Lastly, we determine the RCR, P/O, membrane potential,SDH, Na+/K+ ATPase,Ca2+- ATPase of intestinal mitochondrion, to research the mechanism of intestinal and mitochondrion injury after THIR.Method:We have established the model of total rat liver ischemia-reperfusion 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, eighty Wistar rats were divided into ten groups, eight rats in each group:control; ischemia 20min; FK506,Spiron, MP, NaHS control and 20min+6h interventianal group.The H2S, MDA, Angll, ALD, TNF-a in blood, and the activity of CSE,the content of ICAM-1, NF-κB, CaN in intestinal tissue are determined. 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. Light and electron microscope was used to observe the pathological change of the intestine.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 and ICAM-1,NF-κB,CSE in intestine were significantly increased after ischemia-reperfusion, and reached the peak at about 2-24h. The level of ALD in plasma and intestine, the content, activity and mRNA of CaN in intestine 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 reperfusion. 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 intestinal 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 intestine, and the most serious time is at the 6 hours after ischemia-reperfusion. The mechanism may be involved in the activating of neutrophil and inflammatory cytokines, excess oxidative stress, 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 intestinal injury after ischemia-reperfusion.
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