药物研究
DOU Chunqing;ZHAO Qingchuan;DOU Kefeng;YANG Yanling;YUE Shuqiang;LI Kaizong
2004, 23(8): 519-0521.
To study the effect of tarcrolimus(FK506) on serum TNFα and IL1β levels during inflammatory reactions induced in mice and rats. Methods：80 mice of the Kunming strain and 48 SD rats were randomly divided equally into 2 groups, the acute inflammatory injury (AII) group and tacrolimus pretreatment (AII＋FK506) group, respectively. An endotoxin shock model in mice was wrought by an intraperitoneal injection of LPS( 25 mL·kg1 for each mouse )and a severe acute pancreatitis (SAP) model in rats was produced by a retrograde injection of sodium taurocholate solution(0.8 mL·kg1 for each rat) into the biliopancreatic duct. Beginning from 2 days before the production of the models, mice and rats of the AII＋FK506 group were given each by gastrogavage 20 mL·kg1 of tacrolimus q.12.h., while animals of the AII group were given each equal amount of 0.9% sodium chloride solution in the same manner. 10 mice and 6 rats of both groups were sacrificed 0, 3, 6 and 9 hours after the injection of LPS and sodium taurocholate, respectively. Blood samples were collected and serum TNFαand IL1β contents were determined. The ratio of the wet weight and dry weight (W/D) of the lung was calculated and the histopathology of the lung was studied. Results：A trend of an early rise followed by a subsequent fall in the levels of serum TNFα and IL1β was demonstrated in blood samples from both groups. Serum TNFα and IL1β reached their peaks 3 h and 6 h after the injection of LPS and sodium taurocholate, respectively. The levels of serum TNFα and IL1β were lower in animals of the AII＋FK506 group than those of the AII group at every time point(P＜0.01). The W/D ratio of the lung in animals of both groups 3, 6 and 9 h after the production of the model was greater than that 0 h after the production (P＜0.01). However, the W/D ratio increment was smaller in animals of the AII＋FK506 group than that of the AII group(P＜0.01). Histopathologic examination revealed extensive lesions in parenchymal and interstitial tissues of the lung in animals of the AII group. The interalveolar septa were edematous and thickened. The alveolar architecture was deranged, with the presence of large amount of inflammatory exudates and infiltration of polymorphonuclear neutrophil leukocytes. In contrast, the lung tissue was injured to a much smaller extent in animals of the AII＋FK506 group.Conclusion：Tacrolimus pretreatment was shown to decrease the serum contents of TNFα and IL1β during inflammatory reactions in mice and rats and alleviate the acute lesions induced by inflammatory mediators.
