Effect Of NF-κB Inflammatory Pathway On Intestinal Mucosa Injury In Obstructive Jaundice And Internal And External Drainage In Mice

Background:Obstructive jaundice may compromise the function of intestinal barrier and injure intestinal mucosa possibly via repression of NF-κB pathway.Here,we investigated the expression of NF-κB and their pathway in distal ileum of mice during the progress of obstructive jaundice and its release by biliary internal and external drainage.Methods:In the first part,c57BL/6J mice were allocated into 3 groups:(Ⅰ)sham operation(SH);(Ⅱ)Bile duct ligation(BDL);(Ⅲ)Control(C).Biochemical index as TB,ALT,AST,ALP and endotoxin in serum were detected.The morphological changes of distal ileum tissue were observed using HE staining.Western bolt,Real-time PCR,Immunofluorescence and immunohistochemistry were selective utilized to observe the expression of transcription factor(NF-κB),inflammatory cytokines(TNF-α,IL-6,IL-1β,caspase-8 and caspase-3 of distal ileum issue.In the second part,c57BL/6J mice were allocated into 5 groups:(Ⅰ)sham operation(SH);(Ⅱ)7 days obstructive jaundice(7dOJ);(Ⅲ)14 days obstructive jaundice(14dOJ);(IV)biliary internal drainage(ID);(V)biliary external drainage(ED).Detection methods are the same as part 1 to detect the biochemical index,endotoxin in serum,and observe morphological changes and the expression of NF-κB,TNF-α,IL-6,IL-1β,caspase-3 of distal ileum issue.Results:Serum TB and ALT were significantly increased(p<0.01)after bile duct ligation.Compare to SH group the HE staining pathological score showed that OJ aggravated intestinal inflammation and atrophy.Bile duct ligation induced the activation of NF-κB,and increased expression of TNF-α,IL-6,IL-1β and caspase-8 and caspase-3 gradually after operation(p<0.05).Apoptosis was also found to be increased by caspase-8 and caspase-3 detection after bile duct ligation.After biliary obstruction relieved by nternal and external drainage respectively,the intestinal epithelial injury and endotoxin levels in the internal drainage group recovered significantly instead of external drainage.Compare with 7dOJ group,the expression of NF-κB,IL-1β,IL-6 and caspase-3 expression decreased significantly in the ID group while the expression changes in ED group were not obvious.Conclusions:Obstructive jaundice induced the intestinal mucosal injury and apoptosis by the NF-KB-mediated caspase pathway.Bile duct ligation increased activation of NF-κB in ileum mucosal,meanwhile enhanced the expression of inflammatory factors TNF-a,IL-6,IL-10 and promoted the apoptosis of intestinal mucosal cells by the caspase pathway.Internal drainage instead of external drainage could reverse these changes.These results indicated that the biliary internal drainage can restore intestinal injury casued by obstructive juandice by the NF-KB-associated inflammatory and apoptosis pathway.This may be the reason why biliary internal drainage is superior to biliary external drainage.