Expression And Clinical Biological Significance Of HMGB1-RAGE/TLR4-NF-κB Signaling In Hyperlipidemic Acute Pancreatitis

Objective The aim of this study is to determine the expression of high mobility group box 1 protein(HMGB1),receptor for advanced glycation end-products(RAGE),toll-like receptors4(TLR4)and nuclear factor kappa-B(NF-κB)in patients with hyperlipidemic acute pancreatitis(HLAP),and to investigate the relationship between HMGB1-RAGE/ TLR4-NF-κB pathway and the pathogeny,classification and severity of acute pancreatitis.It provides experimental basis for the prevention and treatment of HLAP.Methods A total of 120 serum samples were collected from patients with acute pancreatitis.According to the inclusion and exclusion criteria,95 patients were investigated.Among them,47 patients with HLAP,48 patients with non-hyperlipidemic acute pancreatitis(NHLAP)and 48 healthy controll patients were included in the final analysis.The expression levels of inflammatory factors were measured by enzyme-linked immunosorbent assay(ELISA),including high mobility group box 1 protein(HMGB1),receptor of advanced glycation endproducts(RAGE),toll-like receptors 4(TLR4),nuclear factor kappa-B(NF-κB).The clinical data and laboratory indexes of all patients were entered into the Epi Data database.Using SPSS 22.0 software to analyze the serum levels of HMGB1,RAGE,TLR4 and NF-κB in HLAP and NHLAP groups,and analyze the relationship between HMGB1-RAGE/ TLR4-NF-κB signaling pathway and the pathogeny,classification and severity of acute pancreatitis.Results Compared to the NHLAP group,patients in the HLAP group had a younger age on average,a higher proportion of males(P=0.000,0.025),and a higher proportion of combined diabetes and fatty liver(P=0.001,0.000).Blood amylase,pancreatic amylase and lipase levels in the HLAP group were lower than those in the NHLAP group during the same period(P=0.001,0.036,0.01);blood sodium and blood chloride were lower than those in the NHLAP group on average(P=0.009,0.026);blood glucose and CRP levels were higher than those in the NHLAP group(P=0.000,0.008).There were no significant difference in blood calcium,potassium and phosphorus between HLAP and NHLAP groups.Compared with the healthy controll group,the expression of HMGB1,RAGE,TLR4 and NF-κB were significantly increased in the patients with HLAP and NHLAP(P<0.05).There was no significant difference between HLAP and NHLAP groups(P>0.05).The patients of AP were divided into MAP,MSAP,and SAP three groups for comparison.There were 66 cases of MAP,29 cases of MSAP and SAP.Compared with the patients of MAP,the expression of HMGB1,RAGE,TLR4 and NF-κB were significantly increased in the patients of MSAP and SAP(P=0.012,0.028,0.022,0.046).The patients of HLAP and NHLAP were divided into MAP,MSAP,and SAP three groups for comparison.There were 30 cases of MAP,17 cases of MSAP and SAP in HLAP group.There were 36 cases of MAP,12 cases of MSAP and SAP in NHLAP group.Compared with the patients of MAP,the expression of HMGB1,RAGE,TLR4 and NF-κB were increased in the patients of MSAP and SAP in both of HLAP and NHLAP groups(P>0.05).In comparison between groups,HMGB1 and RAGE expression levels were higher in the HLAP group with MSAP and SAP than in the NHLAP group,and the difference in RAGE expression was significant(P=0.048).Pearson correlation coefficient was used to analyze the relationship between serum HMGB1 and TLR4,RAGE and NF-κB in patients with AP.The results showed that the level of HMGB1 was positively correlated with the relative protein quantification of TLR4(r=0.297,P=0.047),and no significant correlation with RAGE and NF-κB(P>0.05).Correlations between serum HMGB1 and blood glucose,blood calcium and CRP in AP patients were analyzed by using Pearson correlation coefficients,the results showed a positive correlation between serum HMGB1 concentration and CRP(r=0.313,P=0.008),and no correlation between blood glucose and blood calcium(P>0.05).Conclusion HMGB1 may related to the occurrences and development of acute pancreatitis as a mediator of inflammation.HMGB1 binding to RAGE and TLR4 receptors on the surface of immune cells,which could activate the NF-κB pathway by through the downstream pathways to the intestinal immune system.With the aggravation of acute pancreatitis,the expression of HMGB1 was increased.HMGB1 level may be associated with the severity of the hyperlipidemic acute pancreatitis.By detecting serum HMGB1,it may compensate for the deficiency of significant elevation of serum amylase and lipase in the late stage of inflammation,provide new ideas to guide clinical treatment.