The Role And Mechanism Of High-mobility Group Box 1 In Intestinal Mucosal Barrier Injury In Acute Pancreatitis

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Relationship Between Serum High-mobility Group Box 1 and Intestinal Mucosal Barrier Injury in Patients with Acute PancreatitisObjective: By monitoring the dynamic changes of the high-mobility group box 1(HMGB1)and the intestinal mucosal barrier injury in patients with acute pancreatitis,to investigate the role of HMGB1 in intestinal mucosal barrier injury in patients with acute pancreatitis.Methods: 59 patients with acute pancreatitis in our hospital with onset of 24 h were be choosen.And according to the disease,they were be divided into mild acute pancreatitis(MAP,n=26),moderately severes acute pancreatitis(MSAP,n=17),severe acute pancreatitis(SAP,n= 16).20 healthy persons in our hospital at the same time were set as the control group.Venous blood was extracted at the 24 th hour,48 th hour and 72 th hour after onset of the disease.Using the enzyme-linked immunosorbent assay(ELISA)for determination of the serum HMGB1,TLR4(Toll-like receptor 4),TLR9(Toll-like receptor 9),TNF-?(tumor necrosis factor-alpha),IL-6(interleukin 6),DAO(Diamine oxidase).Results: 1.The levels of serum HMGB1,TLR4,TLR9,DAO in the MAP,MSAP,SAP group were significantly higher than those in the control group at the 24 th hour,48 th hour(P < 0.05),and decreased gradually after reaching the peak value at the 48 th hour.At the 72 th hour,The levels of serum HMGB1,TLR4,TLR9 and DAO in the MAP group were not significantly different from those of the control group(P > 0.05),but the MSAP,SAP groups were significantly higher than those of the control group(P < 0.05).2.At different time points,the levels of HMGB1,TLR4,TLR9,TNF-?,IL-6,DAO in each group were MAP <MSAP < SAP,the difference was statistically significant(P < 0.05).3.There is no difference between MAP group and the control group about the level of TNF-?.The level of TNF-?in MSAP group increased at the 24 th hour,but the levels at 48 th hour and 72 th hour were lower than before.The level of TNF-?in SAP group increased at the 24 th hour,and remained high level at 48 th hour and 72 th hour.4.The level of IL-6 in MAP,MSAP group increased at the 24 th hour,then decreased at the 48 th hour and 72 th hour.The level of IL-6 was t highest at the 48 th hour in the group of SAP and decreased at the 72 th hour.5.At the 48 th hour,Serum HMGB1 levels were significantly correlated with serum DAO(r=0.942,P<0.05).Conclusion: HMGB1 may play an important role in the development of intestinal mucosal injury in patients with acute pancreatitis.Part ? The Role and Mechanism of High-mobility Group Box 1 in Intestinal Mucosal Barrier Injury in Mice with Acute Necrotizing PancreatitisObjective: To study the effect and mechanism of HMGB1 in intestinal mucosal barrier injury in mice with ANP.Methods : ANP model was induced by intraperitoneal injection of caerulein 13 times(50 g/kg)and lipopolysaccharide 1 time(15 mg/kg).24 male KM mice,weighing 20-25 g,were randomly divided into 4 groups,the number of each group is 6.Group A: ANP group.Group B: ANP+ anti-HMGB1 neutralizing antibody,after the success of modeling,then intraperitoneal by anti-HMGB1 neutralizing antibody injection(300 g).Group C: ANP + control Ig Y group,after the success of modeling,then intraperitoneal by control Ig Y injection(300 g).Group D: normal control group.12 hours before the start of experiment,the mice were fasting but free to drink water.The animals were sacrificed 12 hours after the model was finished.The pancreas and small intestine were stained with HE.The serum levels of IL-1?,IL-6,TNF-?,DAO and endotoxin core antibody(Endo CAb)in mice were detected by ELISA.TUNEL assay was used to observe the apoptosis of intestinal epithelial cells.The expression of HMGB1,TLR4,TLR9,NF-?B(nuclear factor-kappa B)in small intestine was detected by Western blot.Results: 1.The mice pancreas of A,B,C group were consistent with sacute necrotizing pancreatitis pathological performance,the pancreas of D group was normal.Compared with A and C group,the pancreatic pathological score of group B was improved.2.Compared with A and C group,the intestinal pathological score of group B was also improved.3.The serum levels of IL-1?,IL-6,TNF-?,DAO and Endo CAb in A,B,C group were significantly higher than group D(P < 0.05).The serum level of group B was significantly lower than A,C group(P < 0.05).There was no significant difference between the group A and the group C(P > 0.05).4.The IOD values in A,B,C group of intestinal mucosal apoptosis detection was significantly higher than the group D(P < 0.05).The IOD value of group B was significantly lower than A and C mice(P < 0.05).There was no significant difference in IOD value between A and C group(P > 0.05).5.The expression of HMGB1,TLR4,TLR9,NF-?B in A,B,C group were significantly higher than that in group D(P < 0.05).The expression of group B was lower than that of A and C mice(P < 0.05).There was no significant difference in protein expression between A and C group(P > 0.05).Conclusions: 1.HMGB1 may play an important role in the intestinal mucosal barrier injury in ANP.2.HMGB1 may activate NF-?B through TLR4 and TLR9 signaling pathway,which may lead to intestinal mucosal barrier damage in ANP mice.3.HMGB1 neutralizing antibody may not only reduce the level of serum inflammatory factors in ANP,but also may protect the intestinal mucosal barrier injury of ANP.