The Study Of Protective Effects Of Edaravone On Pancreas And Kidney Injury Of Rats Severe Acute Pancreatitis

Objective:By establishing severe acute pancreatitis(SAP) model in Sprague-Dawley rats,we observe the pathology changes of pancreas and kidney, The levels of MDA andSOD in the pancreas and kidney tissue, the expression of NF-κB. In our study, weexpect to investigate the effect of Edaravone on SAP oxygen free radical and cytokineof pancreas and kidney injury and explore the mechanism.Methods:Sixty adult male Sprague-Dawley rats were randomly divided into three groups:control group(group C), severe acute pancreatitis group(group S) and treatment groupwith Edaravone (group T). Each group was randomly divided into two subgroups asthe phases of6h、12h after operation. Rats in group S were induced by the retrogradeinjection of bilio-pancreatic duct with5%sodium taurocholate(0.1ml/100g), group Twere injected Edaravone (3mg/kg) immediately in the tail vein after molding, group Swere injected isodose physiology saline immediately in the vein after molding. Cavityof group C were closeed after laparotomy flip duodenum, spile in pancreatic duct, noinjection of sodium taurocholate, and the remaining steps same with model group,Kill and dissect the rats at6、12h time points, observe the change of the pancreas andkidney, The blood samples were harvested, measure the serum amylase (AMY)、bloodurea nitrogen (BUN) and creatinine (Cr) by fully automated analyzer, ELISA detecttumor necrosis factor-alpha(TNF-α) and interleukin-6(IL-6). the tissues samplesincluding pancreas and kidney were harvested, detect superoxide dismutase(SOD)activity by xanthine oxidase,malondiadehyde(MDA) content by thiobarbituric acid colorimetric, obtain the pathological changes of pancreas and kidney by HE staining,Expression of NF-κB p65in pancreas and kidney tissues were determined byimmunohistochemical technique. Establish a data base using statistical softwareSPSS13.0, compare mean data by using completely randomized design analysis ofvariance and the correlation analysis, All data were demonstrated by X±SD, P <0.05as significant difference.Results:1. Observation by light microscope：samples of kidney and pancreas have no any ofpathology change in group C. But in group S, Acinous cell necrosis、stromahydropsy、inflammation cells infiltrating could be seen in pancreas specimen;nephric globule stasis and tubular swelling could be seen in kidney specimen. Insome kidney specimen, we find that necrosis cells and cast in nephric tubular;haemorrhage and inflammation cells inflatrating in stroma.These pathology changesaggravates with time prolong; In comparison with group S, the above-mentionedlesions were significantly decreased in group T.2. In comparison with group C, the serum levels of AMS、BUN、Cr、TNF-α、IL-6were significantly increased in group S(P<0.01), the MDA content of thepancreas and kidney tissues were significantly increased in group S(P<0.01), the SODactivity of the pancreas and kidney tissues were significantly decreased in groupS(P<0.01), Compared with group C, the bacterial translocation rate of tissues and thepathological scores of pancreas and kidney tissue injury were markedly increased ingroup S(P<0.01).3. Expression of NF-κB p65in pancreas and kidney tissues in group C wasalmost not detected, but overexpression of NF-κB p65could be observed in group S（P<0.01）,and increase with time（P<0.01）.4. Pearson correlation analysis revealed: there were positive correlation betweenthe level of MDA with pathological scores and Expression of NF-κB p65in pancreasand kidney tissues (r=0.910、P<0.01，r=0.923、P<0.01；r=0.850、P<0.01，r=0.885、P<0.01); SOD was negatively correlated with pathological scores and Expression ofNF-κB p65(r=-0.891、P<0.01，r=-0.883、P<0.01；r=-0.865、P<0.01，r=-0.841、P<0.01); pathological scores of pancreas tissues was positively correlated with kidneytissues(r=0.952,P<0.01); Expression of NF-κB p65in pancreas and kidney tissues were positively correlated with TNF-α and IL-6(r=0.859、P<0.01，r=0.932、P<0.01；r=0.874、P<0.01，r=0.842、P<0.01).5. In comparison with group S, the serum levels of AMS、BUN、Cr、TNF-α、IL-6were significantly decreased in group T(P<0.01), the MDA content of thepancreas and kidney tissues were significantly decreased in group S(P<0.01), theSOD activity of the pancreas and kidney tissues were markedly increased in groupS(P<0.01), Compared with group T, expression of NF-κB p65and the pathologicalscores of pancreas and kidney tissue injury were significantly down-regulated ingroup S(P<0.05).Conclusions:1. Edaravone has a therapeutic effect on rats severe acute pancreatitis, There aresome possible mechanisms: one can be inferred that Edaravone may inhibit oxygenfree radical production and down-regulate the expression of NF-κB p65so as toalleviate injury and systemic inflammatory response, another can be deduced thatEdaravone may decrease the level of TNF-α and IL-6.2. Edaravone have the protective effects on kidney injury caused by severe acutepancreatitis in rats. It is possible that edaravone can clean up oxygen free radical，inhibit NF-κB p65activities，reduce TNF-a or other cytokines in rat kidney andinhibit injury and inflammatory response.