OBJECTIVE To observe the effects of Lycium barbarum polysaccharide(LBP) intervention on inflammatory response and oxidative stress in rats with cholestatic liver injury, and provide a basis for its deep development.

METHODS  The cholestatic liver injury(CLI) model was established in rats by α-naphthylisothiocyanate(ANIT) induction. The rats were randomly divided into model group, LBP low-dose group(LBP 170 mg·kg⁻¹), LBP high-dose group(LBP 510 mg·kg⁻¹), positive control(ursodeoxycholic acid 60 mg·kg⁻¹), and normal control group. After continuous gavage of the corresponding medication for 6 weeks, blood and liver tissue samples were collected to detect serum markers of liver injury, white blood cell classification, inflammatory factors, oxidative stress, signal pathway regulatory protein indicators, and histopathological observation scores were performed on liver slices.

RESULTS Compared with the normal control, the model of rats showed significant changes in serum markers of liver injury, blood cell classification, inflammatory factors, oxidative stress, relative expression indicators of signaling pathway regulatory proteins, and histopathological observation scores, with statistical significance(SNK-q test or H-test, P<0.01). Compared with the model group, serum markers of liver injury(γ-GGT, TBA, TBIL and ALT) and blood cell classification indicators(WBC, LYMPH and NEUT) in the high-dose LBP group of rats decreased with statistical significance(SNK-q test, P<0.05), inflammatory factors(TNF-α, IL-6, COX-2 and MCP-1) and oxidative stress index(MDA) decreased, while the activities of SOD and GSH-PX increased(SNK-q test, P<0.05), the expression levels of TLR4, pNF-κB, and MyD88 regulated by the TLR4/pNF-κB pathway were downregulated(SNK-q test, P<0.05), while the expression levels of SIRT1 and Nrf2 regulated by the SIRT1/Nrf2 pathway were upregulated, the histological observation score decreased(SNK-q test, P<0.05), histopathological observation score decreased, with statistical significance(H-test, P<0.01 or 0.05). There was no significant difference in various indicators between the low-dose group of LBP rats and the model group, and the differences were not statistically significant(SNK-q test, P<0.05). Compared with the model group, the positive control showed improvements in some indicators in serum markers of liver injury, white blood cell classification, and oxidative stress, while the histopathological observation score decreased. The differences were statistically significant(H-test, P<0.01 or 0.05).

CONCLUSION LBP has a alleviating effect on inflammation and oxidative stress in rats with CLI, and its mechanism of action may be related to downregulating TLR4/NF-κB and upregulation of SIRT1/Nrf2 pathway signaling transduction.