Study on the Effects of HMGB1-mediated Inflammatory Pathway on Liver Injury Induced by Tripterygium wilfordii / 中国药房

ABSTRACT

OBJECTIVE:To study the effects of high-mobility group box 1 protein(HMGB1) -mediated inflammatory pathway HMGB1-Toll like receptor 4 (TLR4) /nuclear transcription factor κ B(NF-κ B)on liver injury of rats induced by Tripterygium wilfordii,and to provide reference for clarify the mechanism of liver injury induced by T.wilfordii. METHODS:Totally 24 SD rats were randomly divided into blank group(normal saline,i. g. ),T. wilfordii group(16 g/kg by crude drug,i. g. )and neutralizer group(16 g/kg T. wilfordii crude drug i. g. after i. p injection of 100 mg/kg Ammonium glycyrrhizinate solution 3 h),with 8 rats in each group. All rats were treated for consecutive 3 weeks. The serum levels of AST and ALT in rats were detected every week. After the end of medication,the serum levels of HMGB1,IL-1β,IL-2 and TNF-α were detected by ELISA method;the protein expression of HMGB1,NF-κB p65 and TLR4 in liver tissue of rats were detected by Western blot assay. The pathological changes of liver tissue in rats were measured with HE staining method. RESULTS:After 3 weeks of treatment,the serum levels of AST, ALT,HMGB1,IL-1β,IL-2 and TNF-α in rats,the protein expression of HMGB1,NF-κB p65 and TLR4 in liver tissue of rats in T. wilfordii group were significantly higher than blank group and neutralizer group(P<0. 05 or P<0. 01). Hepatocyte edema was found around the central vein of the liver,and circular vacuoles were seen in some hepatic cytoplasm in T. wilfordii group;only varying size of vacuoles were found in a small number of cells in neutralizer group. CONCLUSIONS:T. wilfordii induced liver injury may be associated with the activation of HMGB1-TLR4/NF-κB inflammation pathway.