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Experimental Study Of Protective Effect Of Alanyl-Glutamine In The Ischemia Reperfusion Injury Of Live In Rats

Posted on:2004-10-06Degree:MasterType:Thesis
Country:ChinaCandidate:X ZhangFull Text:PDF
GTID:2144360092995985Subject:Surgery
Abstract/Summary:PDF Full Text Request
In the hepatic surgery, Hepatic ischemia reperfusion injury ( HI-RI) can lead to a series of structural and functional disorders of liver tissue and cause hepatic failure or multiple organ system failure. HIRI is one of the main causes affecting the prognosis of the diseases, success rate of the operations and survival rate of the patients. Although the pathogenesis of HIRI has not been completely understood, most of scholars believe that HIRI is related to free oxygen radicals and calcium overload, et al.In previously studies, lots of methods have been used to pertect liver against HIRI, including ischemia pretreatment, portal blood bypass, partial or transient intermittently inflow occlusion and the others. But these methods are Limited at practice for self - deleterious-ness , localization at clinical practice, increasing complexity of the operations or easy emergence of the complications. At same time some drugs, including calcium antagonists, protease inhibitors and oxygen radical eliminators have been used to pertect liver against injuries, but the effects are not definitive or satisfactory, So it is essential to study furtherly the protection methods against HIRI.Reduced glutathione (GSH) is a important antioxidant-that per-tects tissues from free radical injuries. Studies have demonstrated thatincreasing or maintaining the GSH stores in tissues can attenuate free radical injuries. Heat shock protein 70 (HSP70) is highly conserved and produced by bio - cell subjected to a variety of stress. In cells and tissues, HSP70 is an intrinsic perfection mechanism and can increase the tolerance to against stimuli and preelection effects on injuries. The proctection effects of GSH and HSP70 on HIRI and the related influences are always the focus of clinical and experimental studies.GLN, a conditional essential amino acid , occupies a particular and important role in the metabolism in cells and tissues. Studies indicated that Gin concentration in the blood and tissues was related to the prognosis of the diseases and survival rate of the patients in many severe diseases and stress. Supplementation of Gin cound preserve the structures and functions of tissues, decrease length of hospital stay and improve the prognosis and survival rate. For the low solubility and unstable character, it is usually replaced by alanyl - glutamine dipeptide (Ala-Gin) in clinic.It has beeb reported previously that Gin can pertect tissues from the ischemia reperfusion injuries by preserving tissue glutathione stores, enhancing the expression of HSP70 in skeletal muscle, cardiac muscle and intestines. In liver, However, the related reports were rare about its pertective effects on HIRI or effects on GSH level and HSP70 expression in tissues.In our study, we primarily investigated whether Ala - Gin ( Gin) has a perfection effects on HIRI through observing the effect of Ala -Gin (Gin) on the concentrations of the hepatic biochemical enzymes, and furtherly discussed the possible mechanisms through observing the effect on tissue GSH level and the expression of HSP70 in the HIRI model of rat.Materials and MethodsMale Wistar rats were placed central vena catheter through the right external jugular vein, according to the TPN model of the Third Military Medical University. After 2 hours, rats received 0.9% saline solution by minim pump (2ml/h). After observed for 2 days, rats were randomly divided into Gin (G) group and control (C) group. Rats in G group were received the 3% Ala - Gin solution (2ml/h) through the venous catheter and Rats in C group received 0. 9% saline solution at the same velocity and quantity. All solution was infused for 3 days (48ml/d) . At the seventh day, the rats were anesthetized before all operative procedures, and the abdomen was opened through a median laparotomy and the liver was detached from there ligaments. According to Pringle, s method, total hepatic ischemia with portal congestion was produced by clamping the hepatoduodenal ligament for 30 minutes with a microvascular clamp, and dec...
Keywords/Search Tags:glutamine, ischemia reperfusion injury, glutathione, heat shock protein 70
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