Protective effect of FK506 pretreatment on acute liver injury induced by LPS

    DOU Chunª²Qing, DOU Keª²Feng, ZHAO Qingª²Chuan, YANG Yanª²Ling, YUE Shuª²Qiang, LI Kaiª²Zong

    Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi¬ðan 710033, China

    ¡¾Abstract¡¿ AIM: To study the protective effects of FK506 on acute liver injury induced by LPS. METHODS: Acute liver injury model was developed by intraperitoneal injection of LPS. Experimental mice were randomly assigned to LPS and LPS+FK group. The survival curves of the two groups were plotted and the survival rates were analyzed dynamically. At 0, 0.5, 2, 4, 6 and 8 hours after LPS administration, the serum levels of TNFª²¦Á,ILª²1¦Â, ALT and AST were recorded, respectively, and the liver pathological changes were examined. RESULTS: Seventyª²two hours after LPS injection, the survival rate of LPS group was only 10.00%, while that of LPS+FK group was 46.67%(P<0.01).The serum TNFª²¦Á and ILª²1¦Â levels of both LPS and LPS+FK groups had a tendency of increasing first and then decreasing. The serum TNFª²¦Á level and that of ILª²1¦Â reached their respective peak 2 hours and 4 hours after LPS administration. AT every time point, the TNFª²¦Á and ILª²1¦Â levels of LPS+FK group were lower than those of LPS group. Eight hours after LPS injection, the serum ALT and AST levels of LPS+FK group were (1.06¡À0.15) and (1.21¡À0.13) ¦Ìkat/L respectively, while those of LPS groups were (2.51¡À0.47) and (3.97¡À0.36) ¦Ìkat/L(P<0.01). Histologically, FK506 pretreatment alleviated the acute liver injury induced by LPS, including cell swelling, eosinophilic degeneration and PMN infiltration. CONCLUSION: FK506 pretreatment can decrease the liver lesion induced by LPS and downª²regulate the inflammatory reaction, possibly by decreasing the serum TNFª²¦Á and ILª²1¦Â. ......