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Influence Of Glutamine Infused Continuously Before And During Operation On Hepatic Ischemia Reperfusion Injury In Rats

Posted on:2005-03-06Degree:MasterType:Thesis
Country:ChinaCandidate:K CuiFull Text:PDF
GTID:2144360122490991Subject:Surgery
Abstract/Summary:PDF Full Text Request
Hepatic ischemia reperfusion is a common problem in clinical surgery. It can both cause hepatic injury and lead to multiple organs dysfunction even failure in the whole body. It can also lead to death if serious. Its exact mechanism is still not well known. Generally, it is thought to be related to hypoxic injury during ischemia, injury of vascular endothelial cells and hepatocytes during reperfusion and microcirculatory disturbance secondary to endothelial cell injury, etc.As to the protection of this injury, much experimental and clinical research has been done in recent years and a series of methods have been explored that many kinds of preconditionings as ischemia preconditioning; many kinds of shunts; inhibition of Kupffer's cells and blood coagulation pathway; monoclonal or polyclonal antibodies against many kinds of proinflammatory cytokines and re-combinant products of many kinds of antiinflammatory cytokines; drug protection. But few is able to be used clinically.Glutamine is a conditionally necessary amino acid and has been being gradually thought highly of in recent years. It has been used on study of many aspects such as small intestine-related disease, bone marrow transplantation, cho-lestasis and cholelithiasis, trauma and tumor, and so on. As to ischemia and reperfusion injury of viscera, it has been used on study of models of animal small intestine and hind limb and proved to have protective role on viscera. Our experimental group has also showed that glutamine infused before operation had protective effect on ischemia reperfusion injury of rat liver. But in above studies the administration time was all before operation , while Fukatsu et al used small intestine model of ischemia reperfusion injury in mouse and infused glutamine in-travenously during ischemia, but the data showed that it was detrimental. But if glutamine were continuously infused before and during operation, what impact would it exert on ischemia reperfusion injury of liver, relevant reports have not been shown. So in our study we used rat model of hepatic ischemia reperfusion injury, infusing glutamine continuously from 3 days before operation till the end of ischemia reperfusion to observe the influence of glutamine on ischemia reperfusion injury of rat liver. But free glutamine is not stable and its very difficult to preserve in resolutive state for a long period. While Alanyl-Glutamine( Ala-Gin) is highly resolutive, very stable and can bear hot sterilization. It decomposes quickly to free glutamine and alanine by the action of dipeptidase after being infused intravenously. It has the same role as glutamine of preserving normal glutamine level, improving nitrogen balance and shape of small intestinal mucosa. In our study we use Ala-Gin instead of Gin.Materials and MethodsMale Wistar rats weighing 250-300g were cannulated in right external jugular vein , according to the TPN model of the Third Military Medical University and infused 0. 9%Nacl solution(2ml/h) through minipump. After 1 day observation, the rats were divided randomly into experimental or control group. The rats in experimental group were given 3% Ala-Gin solution while those in control group received 0. 9% Nacl solution all at speed of 2ml/h. The solution was infused continuously until the end of ischemia reperfusion. The rats received lapa-rotomy 4 days after cannulation and the hepatic ischemia reperfusion injury model with portal congestion was produced according to Pringles maneuver. The clip was removed to restore the blood flow after 40 minutes of ischemia. 2ml of blood was drawn from portal vein after 1 hour of reperfusion and the endotoxin level was tested by limulus reagent turbidimetry. 3 ml of blood was drawn from abdominal aorta to test the level of serous enzymes( ALT, AST,LDH) with auto-biochemical assay instrument. A small piece of liver tissue of right lobe was cut off and placed into 10% neutral formaldehyde solution for fixation and determination of liver ICAM-1 expression was conducted by sp immunohistochemistry. The da-...
Keywords/Search Tags:Glutamine, liver, ischemia reperfusion injury, barrier
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