Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor

Objective:This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease(CD)regulated by moxibustion through bile acid(BA)enterohepatic circulation and intestinal farnesoid X receptor(FXR).Methods:Sprague-Dawley rats were randomly divided into control group,CD model group,mild moxi-bustion group and herb-partitioned moxibustion group.CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu(ST25)and Qihai(CV6).The changes in CD symptoms were rated according to the disease activity index score,the serum and colon tissues of rats were collected,and the pathological changes in colon tis-sues were observed via histopathology.Western blot,immunohistochemistry(IHC)and immunofluores-cence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.Results:Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD,inhibited inflammation and repaired mucosal damage to the colon in CD rats.Meanwhile,moxibustion could improve the abnormal expression of BA in the colon,liver and serum,downregulate the expression of interferon-y and upregulate the expression of FXR mRNA,and inhibit Toll-like receptor 4(TLR4)and mye-loid differentiation factor 88(MyD88)mRNA.The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression.Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR.Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-KB p65.In particular,herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.Conclusion:Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA,activating colonic FXR,regulating the TLR4/MyD88 pathway,inhibiting intestinal inflammation and repairing the intestinal mucosal barrier.Herb-partitioned moxi-bustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation.