1.Repair mechanism of Echinetin on intestinal mucosal barrier damage in severe acute pancreatitis based on HMGB1/TLR4/PKR pathway
Manhe ZHANG ; Kejing YU ; Shihao JIA ; Fumei ZHANG ; Jingcha HAO
International Journal of Laboratory Medicine 2025;46(2):146-150,156
Objective To explore the effect of Echinetin(ECH)pretreatment on alleviating intestinal bar-rier dysfunction caused by severe acute pancreatitis(SAP).Methods Totally 36 rats were randomly divided into Sham group,SAP group and SAP+ECH group,with 12 rats in each group.Pancreatitis was induced by retrograde injection of 3%sodium taurocholate into pancreatic duct.Histological examination was performed on the pancreas of experimental rats to determine whether the pancreatitis model of rats was successfully con-structed.Intestinal barrier function was evaluated by intestinal pathological scores,serum diamine oxidase(DAO)activity and endotoxin levels,and bacterial translocation in mesenteric lymph nodes.The mRNA and protein expression levels of tight junction proteins ZO-1 and occludin were detected by quantitative fluorescent PCR(qPCR)and Western blot,and the protein expression levels of high mobility frame-1 protein(HMGB1),Toll-like receptor 4(TLR4)and protein kinase R(PKR)were detected by Western blot.Results ECH had no significant effect on the histological changes of pancreas,but could improve the intestinal mucosal barrier damage and membrane permeability associated with SAP.Although ECH does not affect the mRNA expres-sion levels of ZO-1 and occludin in ileum of SAP rats,it could significantly increase the expression levels of ZO-1 and occludin,and ECH treatment could significantly reduce the expression levels of HMGB1,TLR4 and PKR in ileum of SAP rats.Conclusion ECH can reduce the intestinal barrier dysfunction induced by SAP,and its effect on intestinal barrier function may be related to the inhibition of the HMGB1/TLR4/PKR pathway.
2.The Predictive Value of Gut Metabolite Levels for Myocardial Injury and Prognosis in Patients with Acute Pancreatitis
Shihao JIA ; Kejing YU ; Manhe ZHANG ; Fumei ZHANG ; Jingcha HAO
Journal of Kunming Medical University 2025;46(9):137-144
Objective To investigate the value of gut metabolites in predicting the development of severe acute pancreatitis(SAP),myocardial injury,and adverse outcomes in patients with acute pancreatitis(AP).Methods A total of 80 SAP patients admitted to Cangzhou Hospital of Integrated Chinese and Western Medicine from April 2023 to April 2024 were selected as the severe group,and 80 non-severe AP patients were selected as the non-severe group.The levels of serum amylase,lipase,acetic acid,propionic acid,butyric acid,and total short-chain fatty acids(SCFAs)in feces,serum bile acid(BA),trimethylamine n-oxide(TMAO),myocardial injury-related indicators[creatine kinase isoenzymes(CK-MB),cardiac troponin T(cTnT),N-terminal pro-b-type natriuretic peptide(NT-proBNP)],C-reactive protein(CRP),acute physiology and chronic health evaluation II(APACHE II)and bedside index for severity in acute pancreatitis(BISAP)were compared between the two groups at admission.Patients in the severe group were followed up for 30 days and divided into a survival subgroup(n=61)and a non-survival subgroup(n=19)based on their prognosis.The levels of total SCFAs,BA,and TMAO were compared between these two subgroups.Spearman correlation analysis was used to analyze the correlation of serum amylase,lipase,total SCFAs,BA,and TMAO levels with myocardial injury-related indicators and disease severity scores in all patients.Multivariate logistic regression analysis was used to identify the influencing factors for the occurrence of SAP.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of total SCFAs,BA,TMAO,and their combination for the occurrence of SAP.Results Compared with the non-severe group,the severe group had significantly lower levels of acetic acid,propionic acid,butyric acid,and total SCFAs(P<0.01),and significantly higher levels of BA,TMAO,CK-MB,cTnT,NT-proBNP,CRP,and APACHE II and BISAP scores.Within the severe group,the non-survival subgroup had significantly lower levels of total SCFAs(P<0.05)and significantly higher levels of BA and TMAO(P<0.05)compared to the survival subgroup.Spearman analysis showed that the levels of CK-MB,cTnT,NT-proBNP,CRP,and the APACHE II and BISAP scores were negatively correlated with total SCFAs levels and positively correlated with BA and TMAO levels(P<0.001).Multivariate logistic regression analysis revealed that total SCFAs,BA,and TMAO were independent influencing factors for the occurrence of SAP(P<0.05).ROC curve analysis showed that the area under the curve(AUC)for total SCFAs,BA,TMAO,and their combination in predicting the occurrence of SAP were 0.951,0.797,0.790,and 0.974,respectively(P<0.001).The AUC for the combination of the three markers was larger than that of any single marker,indicating good predictive efficacy.Conclusion The levels of gut metabolites SCFAs,BA,and TMAO in SAP patients are independent factors associated with myocardial injury and prognosis.

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