ABSTRACT
OBJECTIVE：To inv estigate the effects of 4-hydroxy-2（3H）-benzoxazolone on inflammatory and apoptosis signaling pathways in non-alcoholic fatty liver disease （NAFLD）model rats. METHODS ：SD rats were divided into normal control group（10 rats）and modeling group （50 rats）. Normal control group was given basic diet ，and modeling group were given high-fat diet to induce NAFLD model. After modeling ，the rats were divided into normal control group ，model group ，silibinin group （26.25 mg/kg），and 4-hydroxy-2（3H）-benzoxazolone high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 8 rats in each group. Normal control group and modeling group were given 0.6％ CMC-Na intragastrically ，and other groups were given relevant medicine 10 mL/kg intragastrically ，once a day ，for consecutive 4 weeks. After last medication ，the serum levels of albumin（ALB），total protein （TP），globulin（GLB），ALB/GLB and free fatty acid （FFA）were detected ；TUNEL staining was used to observe the apoptosis of rat hepatocytes. Western blot assay was used to detect the protein expression and phosphorylation level of inflammatory signaling pathway related proteins [Toll-like receptor 4（TLR4），myeloid differentiation factor 88（MyD88）， nuclear factor-κB p65（NF-κB p65），NF-κB inhibitor protein（IκBα）] in liver tissue as well as the expression of apoptosis signaling pathway related proteins [B cell lymphoma 2（Bcl-2），Bax，caspase-3]. RESULTS ：Compared with model group ，serum levels of TP （except for low-dose group ），GLB and FFA ，the protein expression of TLR 4（except for low-dose group ），MyD88 （except for medium-dose group ）and caspase- 3，the phosphorylation levels of NF-κB p65 and IκBα protein were decreased significantly（P＜0.05 or P＜0.01）. The ratio of A LB/GLB in serum and the ratio of Bcl- 2/Bax in liver tissue were significantly increased（P＜0.05 or P＜0.01），and the phenomenon of hepatocyte apoptosis was improved. CONCLUSIONS ：4-hydroxy-2 （3H）-benzoxazolone can ameliorate NAFLD in rats ，and the mechanism may be associated with inhibiting the expression TLR 4/ MyD88/NF-κB signaling pathway-related proteins and apoptosis-related proteins in liver tissues.
ABSTRACT
OBJECTIVE：To s tudy improvement effect and mech anism of ilicifoliosids alkaloid A （HBOA）on non-alcoholic fatty liver disease in rats. METHODS ：SD rats were randomly divided into blank control group ，model group ，Silybin capsule group（positive control ，26.25 mg/kg），HBOA high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 10 rats in each group. Except that blank control group fed normal feed ，the other groups were continuously fed with high-fat diet for 8 weeks to induce non-alcoholic fatty liver disease model. Form the 9th week ，blank control group and model group were given constant volume of 0.6％ CMC-Na solution ，and administration groups were given corresponding drugs by intragastric admini- stration，once a day ，for consecutive 4 weeks. The general information of rats were observed and the body weight increase ，organ （liver，kidney and spleen ）indexes were calculated ；the contents of AST ，ALT，TC，TG and NEFA in liver tissue were detected ， and SOD，GSH-Px activities and MDA content in the serum were also determined. The protein expression of PPARα in liver tissue was detected by immunohistochemistry. RESULTS ：Compared with blank control group ，the body mass increase and liver index of rats in model group were increased significantly （P＜0.01）；fat deposition could be observed in the liver ；the activities of SOD and GSH-Px in serum were reduced significantly ，and the contents of MDA ，the contents of AST ，ALT，TC，TG and NEFA in liver tissue were significantly increased ，and the protein expression of PPARα was decreased significantly（P＜0.01）. Compared with model group ，the body mass increase and liver index of the rats were decreased significantly in administration groups （P＜0.05 or P＜0.01），liver fat deposition was improved ，the activity of SOD and GSH-Px in serum （except for HBOA low-dose group ）were increased significantly while MDA content ，the contents of AST ，ALT，TC（except for HBOA low-dose group ），TG（except for HBOA low-dose group ） and NEFA in liver tissue were decreased significantl y，while protein expression of PPAR α 15177460685@163.com was increased significantly （P＜0.05 or P＜0.01）. Some of the above indexes of HBOA high-dose group were 电话：0771-5302433。E-mail：junlin898@126.com significantly better than HBOA medium- and low-dose group（P＜0.05）. CONCLUSIONS ：HBOA has a certain improvement effect on non-alcoholic fatty liver disease in rats caused by high-fat diet ，and its mechanism may be related to improving lipid metabolism disorders ，anti-oxidative stress and up-regulating the expression of PPARα.