关键词: 低分子壳聚糖, 四氯化碳, 肝纤维化, Toll样受体4

Abstract:

Abstract:ObjectiveTo clarify the inhibitory effect of low molecular weight chitosan（LMCTS）on hepatic fibrosis induced by carbon tetrachloride (CCl4) in the rats,and to investigate its effect on the expression of Toll-like receptor-4(TLR4) and to lay the foundation for the development of the clinical candidate drug of liver fibrosis.Methods 72 male Wistar rats were randomly divided into blank control group,CCl4 group(model group),glycyrrhizinate (DG) group,50,100 and 150 mg/kg LMCTS groups (low,middle and high doses of LMCTS groups).In addition to  blank control group,the rats in the remaining groups were given 40% CCl4-vegetable oil (1.75 mL/kg),2 times per week for 8 weeks,by intraperitoneal injection to establish the model of rat hepatic fibrosis.And the rats in blank control group were injected with the same amount of 100% vegetable oil agent.From the ninth week，the rats in DG and LMCTS groups were given DG and LMCTS by intragastric administration,1 time/week for 4 weeks.Then all rats were sacrificed,the activities of serum glutamic acid aminotransferase (ALT),aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected with ELISA kit;the pathological changes in liver tissue were observed under light microscope,and the TLR4 expressions were detected by RT-PCR and Western blotting method.Results The serum ALT,AST and ALP activities in middle and high doses of LMCTS groups were lower than those in model group  (P<0.05).The serum ALT activity in middle dose of LMCTS group was lower than that in low dose of LMCTS group (P<0.05),but the activities of AST and ALP had no  statistically significant change(P>0.05).There were statistically significant differences in the serum ALT,AST and ALP activities  between high dose of LMCTS group and middle  dose of LMCTS group (P<0.05).There were obvious hepatocyte steatosis,inflammatory cell infiltration,collagen fiber hyperplasia and hepatic lobule damage in the rats in model group.However,all the  changes in liver tissue of the rats in LMCTS group  were significantly reduced,especially in high dose group.The results of RT-PCR and Western blotting method showed that the expression of TLR4 was declined in LMCTS groups compared with model group (P<0.05,P<0.01),especially in high dose of LMCTS group,and there were statistically significant differences between  different doses of LMCTS groups (P<0.05).Conclusion High dose of LMCTS can decrease the serum transaminase activity of liver fibrosis rats and improve liver function,and this process may be related to declining the expression of TLR4.

Key words: low molecular weight chitosan；carbon tetrachloride, hepatic fibrosis；Toll-like receptor 4