ABSTRACT
OBJECTIVE： To observe the improvement effect and mechanism of 4-hydroxy-2-benzoxazolone （HBOA） on carbon tetrachloride-induced hepatic fibrosis in rats. METHODS： Male SD rats were randomly divided into normal control group， model group， colchicine group （positive control， 0.4 mg/kg） and HBOA low-dose， medium-dose and high-dose groups （50， 75， 100 mg/kg）， with 12 rats in each group. Except for normal control group was given constant volume of normal saline intragastrically， other groups were given 50％CCl4-olive oil solution （2 mL/kg， initial dose double） intragastrically， twice a week， for consecutive 12 weeks， to induce hepatic fibrosis model. Since the 9th week of modeling， administration groups were given relevant medicine intragastrically. Normal control group and model group were given constant volume of 0.6％ Carboxymethylcellulose sodium solution intragastrically， once a day， for consecutive 4 weeks. After last administration， the serum contents of ALT， AST， IL-1β and IL-10， the protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissue were determined. RESULTS： Compared with normal control group， the positive expression of NF-κB p65 in liver tissue was increased significantly in model group； serum contents of ALT， AST and IL-1β as well as protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissure were increased significantly， while serum content of IL-10 was decreased significantly （P＜0.05）. Compared with model group， the positive expression of NF-κB p65 in liver tissue were decreased to different extents in administration groups； serum contents of ALT， AST and IL-1β as well as protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissue were decreased significantly， while serum content of IL-10 was increased significantly （P＜0.05）. CONCLUSIONS： HBOA can improve carbon tetrachloride-induced hepatic fibrosis in rats， and the mechanism of which may be associated with relieving inflammatory reaction by blocking NF-κB signaling pathway and down-regulating the protein expression of ICAM-1.
ABSTRACT
Aim To investigate anti-hepatic fibrotic mechanism of Acanthus ilicifolius alkaloid A ( HBOA ) involved in high mobility group box 1 ( HMGB1 ) . Methods A hepatic fibrosis model of rat was estab-lished by the olive oil of CCl4 for 12 weeks. Then, at the 8th week,the successful model rats were randomly divided into model control group, colchicine group, HBOA high-dose group and HBOA low-dose group. From the 9th week,the rats in each group were treated with the drugs daily for 4 weeks respectively. The changes of liver histopathology and collagen were ob-served by HE staining and Masson staining, and the serum indicators including aspartate aminotransferase (AST),alanine aminotransferase(ALT) , total biliru-bin ( T-BIL ) , HMGB1 , interleukin-1β( IL-1β) and tumor necrosis factor-α( TNF-α) were determined. Moreover , the protein of HMGB1 in liver was examined by immunohistochemistry, and the expression of HMGB1 mRNA was measured by real-time fluores-cence quantitative PCR. Results Compared with the model control group,HBOA high-dose and HBOA low-dose groups significantly attenuated the fibrotic degree induced by CCl4 , markedly decreased the levels of ALT, AST, T-BIL, HMGB1, IL-1β, TNF-α. Moreo-ver, the expression of HMGB1 protein and mRNA in liver was decreased. And furthermore, serum HMGB1 level had significant positive correlation with IL-1β, TNF-α,ALT,AST and T-BIL. Conclusion HBOA has beneficial effects against liver fibrosis in rat which is induced by CCl4 , the mechanisms may be related to the inhibition of inflammatory response to HMGB1 .