免疫抑制剂FK506预处理对内毒素休克的干预作用

Effect of FK506 pretreatment and its mechanism on endotoxin shock induced by LPS

目的 探讨FK5 0 6预处理对内毒素休克的干预作用。方法 以脂多糖 (LPS)诱导内毒素休克小鼠 15 5只为研究对象 ,将实验小鼠随机分为LPS组 (n =80 )、LPS +FK组 (n =75 )。随机抽取LPS组小鼠 2 0只 ,LPS+FK组小鼠 15只进行生存率观察 ,两组剩余小鼠给予LPS注射后 ,分时间段采血 ,剖胸、腹取肺脏及肝脏组织 ,测定肺干重/湿重比值 (W/D) ,血清TNF α、IL 1β和ALT、AST值。HE染色光镜观察肝脏病理改变。结果 与LPS组相比 ,LPS +FK组小鼠平均存活时间明显延长 ,72h存活率达 4 6 .6 % ;各时间点肺干重/湿重比值及血清ALT、AST含量均显著降低 ;血清TNF α、IL 1β含量明显降低 ,肝、肺组织病理学改变明显改善。结论 FK5 0 6预处理可减轻内毒素休克所致的多器官损害 ,具有下调炎症反应的作用。

Objective To study the effect of FK506 pretreatment on endotoxin shock induced by LPS. Methods 155 mice of the Kunming strain were randomly divided into LPS group (n=80) and LPS|FK group (n=75). An endotoxin shock model of mice was reproduced by an intraperitoneal injection of LPS (25ml/kg for each mouse). Beginning from 2 days before the reproduction of the model, each mouse of the LPS+FK group were given 20ml/kg of FK506 q 12 h, by gastric gavage while animals of the LPS group were given an equal amount of 0.9% sodium chloride solution in the same way. The survival time of 20 mice of the LPS group and 15 mice of LPS+FK group was observed. 10 mice of each group were sacrificed at 0,0.5,2,4,6 and 8 hours after the injection of LPS, respectively. Blood samples were collected and serum TNF-α and IL-1β, contents, and activiry of ALT and AST were determined. The ratio of the wet weight and dry weight (W/D) of the lung was calculated, and the histopathology of the lung and the liver was studied. Results The mean survival time was longer and the 72h survival rate in mice of LPS+FK group was higher, but the serum ALT and AST activity and serum TNF-α and IL-1β contents were lower than those of LPS group at each time point. The W/D ratio of the lung in animals of both groups at 4,6 and 8 hours after the injection of LPS was greater than that at 0 hour (P<0.01). However, the W/D ratio in animals of the LPS+FK group showed a smaller increase than that of the LPS group. The histopathological changes in the lung and liver tissue in mice of the LPS+FK group were ameliorated compared with LPS group. Conclusion FK506 pretreatment can decrease the multiple-organ damages caused by endotoxin shock and down-regulate the inflammatory reaction.