Influence Of Ulinastatin On Intestinal Mucosal Barrier In Septic Rat Model

Researching background: Sepsis is a complex syndrome caused by an uncontrolled systemic inflammatory response of infectious origin, always complicated with grave infection, serious wounds, major operation, gravis type acute pancreatitis and shock. Sepsis could develop to septic shock, acute respiratory-distress syndrome and multiple organ dysfunction syndrome. In spite of the conspicuous advancement on anti-infection therapy, surgical technic, danger-advanced disease guardianship and treatment technic, severe sepsis is now considered to be the most common cause of death in non-coronary critical care units. Overseas epidemiologic survey showed that death rate of sepsis had exceeded that of acute myocardial infarction, there were above 350 thousands of people died of the disease in Europe and American, the therapy cost above 25 billions dollars. There were above 18 millions patients of severe sepsis and the amount of patients increased by degrees of 1.5 percent per year.Surviving Sepsis Campaign, an international effort to increase awareness and improve survival in severe sepsis, was initiated by ESICM, ISF,SCCM in October 2002 with the Barcelona Declaration. SSC obtained response from another seven academic societies and organization, and supported by corporation as Baxter,Lilly,Edwards et al.A great deal of investigations from domestic and overseas indicated that the cytokine acted crucial role in the patho-physiological course of sepsis, because of the attack of infection, empyrosis, wounds, operation and so on, inflammation stimulus such as the Bacterial endotoxin, metabolites of ectotoxin, activated excessively inflammation effector cell such as rhagiocrine cell, neutrophilic leukocyte, accordingly induced these cells excessively released inflammative medium such as proinflammatory factors, proteinum zymolases as well as oxygen free radical, cells were damaged and waterfall's magnification effect was brought about, the inflammative balance in vivo was destroyed, facilitation effect exceeded that of inhibition, cell and tissue damage and functional disturbance were aggravated, thus sings and symptoms of sepsis were expressed.Recently, bowels barrier function has became an important index to judge the prognosis of critical patients, intestinal tract was not only the target organ but also the starter of MODS. So it has became an important topic in current medical domain investigation to study of prevention and cure to nonfunction of bowels barrier function , and critical damage of intestinal mucosa barrier induced by serious sepsis could aggravate pyemic variation all the more.Ulinastatin , also called urinastatin, was a broad-spectrum ulinary trypsin inhibitor(UTI) demeshed and depurated from fresh urine of normal adult male, was one of the endogenous substance to restrain phlegmonosis, could restrain the activity of proteolytic enzyme, relieve the liberation of proinflammatory factor, palliate inflammatory reaction, stabilize lysosomal membrane, restrain generation of oxygen free radical and myocardial depressant factor, improve blood circulation, protect cells and tissues. Clinically ulinastatin was used to treat acute pancreatitis , acute episode of chronic pancreatitis, shock, immunological function regulation, and to protect the function of critical organ during the operation of liver and kidney transplant and ischemical reperfusion trauma caused by extracorporeal circulation. It was proved by animal experiment that ulinastatin could decrease the death of septic shock animal, but at present, the reports were few whether ulinastatin could improve the indexes from intestinal mucous membrane.Objective:To evaluate ulinastatin's protection and safety to intestinal mucosa of pyemic rats through detecting the sensitive target of intestinal mucosal barrier.Methods: Selecting 40 standard deviation rats, to make sepsis pattern through classical cecal ligation and puncture method, divided equally randomly into four sets: control group(C), ofloxacin group(O), ulinastatin group(U) , ofloxacin and ulinastatin group(O+U). Ofloxacin was used with 8mg/kg in group A, ulinastatin was used with 15×104u in group U(ulinastatin was made in Guangdong Techpool Bio-Pharma Co.,Ltd.), ofloxacin was used with 8mg/kg and ulinastatin was used with 15×104u in the same time in group (O+U), bis in die summendus for two days, normal saline was used with 4ml/kg in group C. Sampling rat's intestinal mucosa to detect malondialdehyde(MDA), superoxide dismutase(SOD)and diamine oxidase(DAO) after treating 24 and 48 hours, to observe the variation of these targets .Results: The intestinal mucosa targets are improved obviously in the three sets rats treated, MDA of intestinal tissue is degraded obviously in the treated sets, the degraded degree is: O0.05).Conclusion: Ulinastatin could restrain the excessive inflammatory reaction significantly, improve the pathogenetic condition of pyemic rats, diminish the release of oxygen free radical, degrade the consumption of SOD, increase the activity of SOD, reduce the generation of MDA, palliate damage to intestinal mucosa barrier , protect the barrier function of intestinal mucosa, increase the activity of DAO in intestinal mucosa. The effect would be better when it is used with Anti-Infective drugs, it is indicated that ulinastatin is safe and reliable, is an important combined therapy means to avoid and prevent the generation and development of MODS and MOF.