The Effect Of Curcumin On Intestinal Barrier Function In Rat With Nonalcoholic Fatty Liver Disease Induced By High Fat Diet

Obejective:To investigate the effect of curcumin on intestinal barrier function in rat with nonalcoholic fatty liver disease induced by high fat diet.Methods:Male Sprague-Dawley rats were randomly separated into two groups:normal normal chow diet, high fat diet. After 12 weeks. To verify nonalcoholic fatty liver disease model established, three rats in the high fat diet group were randomly executed. The remaining rats were randomly divided into three groups:normal chow diet (NC). high fat diet (HFD), high fat diet+curcumin (HFD+Cur). The HFD+Cur group was given curcumin 200mg·kg-1·d-1 by gastric perfusion for another 4 weeks. The NC and HFD groups were received 0.5% Cmc-Na in the meantime. All the animals were sacrificed after 16 wk. Hematoxylin & eosin (HE) and oil red staining (ORO) of hepatic tissue was performed. Plasma (lipopolysaccharide, LPS), (transforming growth factor- beta, TNF-uα), (diamine oxidase, DAO) was detected by ELISA. Intestinal epithelial tight junctions were observed by electron microscopy. Occludin and ZO-lin intestinal epithelial cells was detected by immunohistochemistry. Western blots were used for the protein of Toll-like receptors 4 (TLR4), phosphorylated Nuclear Factor-kappa B (p-NF-κB), Occludin expression assays.Results:1.Compared with NC group, the levels of serum aspartate amino transferase (AST), alanine aminotransferase (ALT), liver index and the content of liver fat were significantly increased in the HFD group (P<0.05 vs. NC group); HE and ORO suggested that high fat diet can induce liver steatosis and inflammation.2.Contrast to NC group, the levels of serum DAO. LPS, TNF-a in the HFD group was really higher. electron microscopy analysis demonstrated that tight junctions were significantly destroied in the HFD group, and the protein expression of TLR4/P-NF-κB in the intestinal mucosa significantly increased (P<0.05 vs. NC group). The protein expression of occludin in the intestinal mucosa significantly decreased(P<0.05 vs. NC group);The Immunohistochemistry analysis of NC group showed that occludin was localized to the apical region of the intestinal lateral plasma membrane and distributed in a continuous pattern.3.Compared with HFD group, Curcumin treatment significantly decreased the serum AST and ALT levels, liver index, and liver fat content (P<0.05 vs. HFD group); HE and ORO found that Curcumin treatment alleviated the degree of liver steatosis and inflammation.4.Contrast to HFD group, Curcumin treatment significantly decreased of serum DAO, LPS and TNF-a levels; Electron microscopy analysis demonstrated that tight junctions were significantly shorter in the HFD group than in the Curcumin treatment group. The protein expression of TLR4/P-NF-κB in the intestinal mucosa significantly decreased(P<0.05 vs. HFD group);he protein expression of occludin in the intestinal mucosa significantly increased (P<0.05 vs. HFD group);The Immunohistochemistry analysis of Curcumin treatment group showed that occludin was localized to the apical region of the intestinal lateral plasma membrane and distributed in a continuous pattern.Conclusion:Curcumin could improve NAFLD through protecting the liver function, reducing weight and liver fat deposition. Protection intestinal barrier and decreasing serum inflammation factors by curcumin might played a role in its alleviation of NAFLD. Inhibiting TLR4/P-NF-κB pathway activation by curcumin might help increasing tight junction protein and improve intestinal tract barrier.