Effects Of Internal And External Biliary Drainage On The Expression Of Intestinal FXR And TLR4 In Mice With Obstructive Jaundice

Backgrounds:The study is a series of studies of obstructive jaundice (OJ). Our previous study found that internal biliary drainage (ID) was better than external biliary drainage (ED) in terms of recovery of cellular immune function. Bile acids (BAs) may play a key role in regulation of liver Kupffer cells and intestinal immune system. It is well known that pathogenic pattern recognition receptors (PRRs) play an important role in intestinal immune system. We suppose that BAs can improve intestinal function by regulating the expression of farnesoid X receptor (FXR) and Toll-like receptor (TLR) 4 in the intestinal epithelial cells.Aims:To study the expression of intestinal FXR and TLR4 in mice with OJ and its relief by ID and ED and to explore interaction mechanism between FXR and TLR4.Methods:Sixty male adult Kunming mice were randomly assigned to four groups:OJ, ED, ID, sham operation (SH)(n=15 in each group). On the 9th day from the first operation, the OJ and SH mice were executed and specimens of blood and ileal tissue of groups were collected. So did it On the 9th day from the second operation in ID and ED groups. Blood was drawn from heart for liver function test. The terminal ileum specimen was collected for test of histology using haematoxylin-eosin (HE) staining.Western blot and real-time polymerase chain reaction were used to detect the expression of protein and mRNA of FXR and TLR4 in intestinal mucosa. Moreover, another 40 mice were randomly averaged to four groups-OJ, ED, ID, SH (n=10). Food gavage with FXR agonist-GW4064 was given in 5 mice and vehicle-CMC-Na in another 5 mice in each group.Results: After biliary obstruction, the expression of protein (0.792±0.034) and mRNA (0.902±0.072) of FXR were significantly increased compared with SH group's (0.407±0.072 and 0.315±0.081 respectively) (OJ vs SH, both P<0.001). The expression of protein (0.294±0.065) and mRNA (0.097±0.063) of TLR4 were significantly decreased compared with SH group's (0.729±0.125 and 0.546±0.044 respectively) (OJ vs SH, both P<0.001). After ED, compared with OJ group's, the expression of protein (0.675±0.046) of FXR was decreased while mRNA (0.972±0.233) was incresed (ED vs OJ, P=0.001 and P=0.519) and the expression of protein (0.421±0.050) and mRNA (0.194±0.022) of TLR4 were increased (ED vs OJ, P=0.018 and P=0.021). After ID, the expression of protein (0.524±0.021) and mRNA (0.679±0.010) of FXR were significantly decreased compared with OJ group's (ID vs OJ, P<0.001 and P=0.066), but were still higher than that in SH group (ID vs SH, P=0.002 and P=0.008) and were better than ED group's (ID vs ED, P<0.001 and P=0.023). And the expression of protein (0.524±0.021) and mRNA (0.397±0.023) of TLR4 were significantly increased compared with OJ group's (ID vs OJ, both P<0.001), but were still lower than that in SH group (ID vs SH, P=0.007 and P=0.002) and were better than ED group's (ID vs ED, P=0.006 and P<0.001). The trend of TLR4 expression was almost the same between vehicle group and no gavage group. After gavage with FXR agonist, the differences of TLR4 expression of four groups disappeared (P>0.05).Conclusion:The expression of intestinal FXR was increased while TLR4 was decreased in mice with obstructive jaundice. These changes could be reversed by relief of jaundice, but internal biliary drainage was better than external drainage. Bile acids in the intestine play a key role underlying the mechanism of the changes.