The Evaluation Value Of LDH Isozyme HBDH On The Severity Of Acute Pancreatitis And The Protective Effect Of LDH Inhibitors In Mice With Acute Pancreatitis

Acute pancreatitis(AP)is a kind of disease caused by inflammatory reaction,which can result in pancreatic acinar cell injury,interstitial edema and hemorrhage,and also leads to local and systemic complications.80%of AP are self-limiting and have a good prognosis and the remainder progresses to Severe acute pancreatitis(SAP).Although the diagnosis and treatment technology is greatly improved,the mortality rate of SAP is still as high as 5-20%Therefore,there is an urgent need for a novel,simple and effective evaluation method,or indicator to predict the severity of AP.Studies have shown that LDH is closely related to inflammation related diseases and organ failure.Circulating LDH level can reflect the prognosis of acute myocardial infarction At present,LDH has been included in the Ranson scoring system to evaluate the severity of AP.α-hydroxybutyrate dehydrogenase(HBDH)is an isoenzyme of LDH,which mainly represents activity of LDH1 and LDH2.Because LDH are widely distributed in human tissues and lack specificity.Recently,scholars have paid more attention to the clinical value of LDH isoenzyme HBDH.Whether circulating HBDH level changes significantly in AP and whether it has predictive value in AP has not been reported.In addition,LDH inhibitors have been approved for clinical treatment of epilepsy and inhibition of tumor growth and metastasis.It is not clear whether LDH inhibition can be a potential therapeutic target for AP Therefore,the purpose of this study is:① To explore the evaluation value of serum HBDH on the severity of AP;② To evaluate the therapeutic effect of stiripentol,an LDH inhibitor,in mice with AP induced by caeruleinThis study is divided into the following two parts:Part I:To explore the evaluation value of serum HBDH on the severity of AP Objective:To investigate the value of serum hydroxybutyrate dehydrogenase(HBDH)level,an isozyme of lactate dehydrogenase(LDH),in the evaluation of the severity of acute pancreatitis(AP).Methods:Patients diagnosed with AP from January 2013 to December 2018 were included in this retrospective study.Patients were divided into the normal serum HBDH levels group(n-HBDH group)and the high serum HBDH levels group(h-HBDH group)according to the HBDH≥182U/L after admission.The demographic parameters,laboratory data and the severity of AP in the two groups were compared.The receiver operating curve(ROC)was used to evaluate the efficacy of serum HBDH in predicting persistent organ failure and systemic inflammatory response syndrome(SIRS).Results:A total of 260 AP patients were enrolled,including 176 cases in the n-HBDH group and 84 cases in the h-HBDH group.The incidence of SIRS and organ failure in the h-HBDH group were significantly higher than those in n-HBDH group(both P<0.001).In addition,the serum HBDH levels were significantly increased in patients with organ failure and SIRS,and were positively correlated with Atlanta classification,Ranson score,and BISAP score(all P<0.05).ROC analysis showed that a serum HBDH cut-off point of 195.0 U/L had optimal predictive value for the development of persistent organ failure(AUC=77.8%)and 166.5 U/L for the development of SIRS(AUC=72.4%).Conclusion:The elevated serum HBDH in early stage closely related to the adverse prognosis of AP patients,which can be used as a potential early biomarker for the severity of AP.The second part:the therapeutic effect of stiripentol,an LDH inhibitor,in mice with AP induced by caeruleinObjective:To evaluate the therapeutic effect of stiripentol,an LDH inhibitor,in mice with AP induced by caeruleinMethods:ICR mice weighing 20-25g were divided into control group,model group and model+SPT group.Mice ware intraperitoneal injected by caerulein 100ug/kg/h*10 times.Stiripentol,an LDH inhibitor,was given to the stomach of mice one hour before the intraperitoneal injection of caerulein at a dose of 250mg/kg.12 hours after the first injection of caerulein,the mice were killed,and the pancreas and lung tissues were taken for HE and Immunohistochemistry staining to observe the degree of tissue damage and inflammatory cell infiltration.The serum levels of lipase,amylase,LDH and lactate were tested.Results:stiripentol could reduce the histological damage of pancreas and the level of serum amylase and lipase in mice with AP.Also,after the administration of stiripentol,the infiltration of inflammatory cells in pancreas and lung tissue decreased,and the thickness of alveoli and congestion decreased.In addition,compared with the model group,the serum LDH and lactate levels in the administration group were significantly decreasedConclusion:These findings suggest that stiripentol can reduce the level of lactate by inhibiting LDH,thus reducing acinar cell necrosis and the severity of AP,and has protective effect on distant organs,which may provide new therapeutic targets for pancreatic necrosis and distant organ protection of AP.