Succinylaniline Hydroxamic Acid Protects Pancreatic Tissue From Hemorrhagic Shock In Rats

Background:In shock caused by various reasons,the blood perfusion of organs and tissues is decreased or insufficient correspondingly.After the restoration of blood perfusion,excessive free radicals attack the tissue cells that regain the blood supply,thus aggravating the existing structural damage and dysfunction.This phenomenon is called"Ischemia-reperfusion injury"（I/R）^[1].In many clinical environments,"ischemia-reperfusion injury"of the pancreas is a common pathophysiological process.In recent years,many studies have suggested that histone acetylation plays an important role in the process of pancreatic injury and inflammation induced by gallstone,alcohol,hyperlipidemia,ischemia and other factors.In order to solve the problem of clinical treatment of pancreatic injury,we used rats with hemorrhagic shock as a model to evaluate the severity of pancreatic injury after mild and severe hemorrhagic shock,and to explore the protective effect of succinylaniline hydroxamic acid（SAHA）on pancreatic injury in the rat hemorrhagic shock model,so as to provide a new perspective and target for the study of pathophysiological mechanism of pancreatic inflammatory injury and the development of clinical related therapeutic drugs.Methods:Randomly,We divided 72 SD rats into sham operation（Sham）group（n=12）,sham operation SAHA intervention（Sham+SAHA）group（n=12）,mild hemorrhagic shock（MHS）group（n=12）,mild hemorrhagic shock SAHA intervention（MHS+SAHA）group（n=12）,severe hemorrhagic shock（SHS）group（n=12）and severe hemorrhagic shock SAHA intervention（SHS+SAHA）group（n=12）.Mild and severe hemorrhagic shock were induced by 20%and 40%of total blood loss,respectively,and 60min was maintained.After resuscitation,autologous blood and SAHA or carrier fluid were used for resuscitation respectively.Resuscitation lasted for three hours,and then the rats were killed,and the ratio of wet weight to dry weight of pancreas was calculated,and the pathomorphological changes of pancreatic tissue were observed by HE staining,and the degree of histone acetylation and inflammatory cytokines in pancreatic tissue were determined by western blotting.Results:Data analysis showed that in comparison with the sham operation group,under the hemorrhagic shock model,the pancreatic injury score,wet/dry weight ratio,inflammatory factor expression,phosphorylated NF-κB/p65 expression and histone acetylation decreased with the aggravation of shock.Therefore,we think that under the rat shock model,we construct the rat pancreatic injury model,and draw the conclusion that with the increase of the severity of hemorrhagic shock,the degree of pancreatic injury is also aggravated.After the administration of SAHA adjuvant,compared with the data,especially in the severe shock group,it was found that the pancreatic pathological injury score,wet/dry weight ratio,the content of inflammatory factors and the level of activated NF-κB/p65decreased,while the expression of acetylated H4 was promoted.Thus we concluded that under the rat model of pancreatic injury induced by hemorrhagic shock,the intervention of SAHA adjuvant can effectively inhibit the pancreatic injury induced by hemorrhagic shock-reperfusion in rats and play its protective role.Conclusion:SAHA intervention can significantly reduce pancreatic injury induced by hemorrhagic shock-reperfusion in rats and protect pancreatic tissue.The mechanism may be related to the reversal of histone acetylation and inhibition of NF-κB pathway.