他克莫司对炎症反应血清TNF-α、IL-1β含量的影响

Effect of Tacrolimus on Serum TNF-α and IL-1β Levels during Inflammatory Reactions Induced in Mice and Rats

目的 :探讨他克莫司 (FK5 0 6)预处理对炎症反应血清肿瘤坏死因子 (TNF α)、白细胞介素 1β(IL 1β)含量的影响。方法 :以内毒素休克和重症急性胰腺炎造成的急性肺损伤动物作为研究对象。脂多糖 (LPS)腹腔注射法诱导内毒素休克小鼠模型 ,牛磺胆酸钠胰胆管逆行注射法建立大鼠重症急性胰腺炎 (SAP)模型。实验动物随机分为AII组、AII +FK5 0 6组 ,实验前 2d开始 ,AII +FK5 0 6组动物给予他克莫司 2 0mL·kg 1 ,sc ,每 12h给予相同剂量维持 ;AII组以 0 .9%氯化钠注射液替代他克莫司。分别测定 0 ,3 ,6,9h两组血清TNF α、IL 1β含量并观察肺湿重 干重 (W D)比值 ,肺组织病理学改变。结果 :两组血清TNF α、IL 1β含量均呈先升后降趋势 ,TNF α于 3h达峰值 ,IL 1β于 6h达峰值 ,各时间AII +FK5 0 6组TNF α、IL 1β含量均较AII组低 ,均差异有极显著性 (均P <0 .0 1) ;各时间点AII、AII +FK5 0 6组大、小鼠W D比值均较 0h相显著升高 ,AII +FK5 0 6组升高幅度低于AII组 ,均差异有极显著性 (均P <0 .0 1)。肺组织病理显示 :AII组大小鼠肺实质及间质广泛性损害 ,肺间隔明显水肿、增厚 ,肺泡结构紊乱伴大量炎性渗出及PMN浸润 ;AII +FK5 0 6组肺组织损伤程度减轻。结论 :他克莫司干预可减少炎症反应时血清TNF

Objective:To study the effect of tarcrolimus(FK506) on serum TNF-α and IL-1β 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·kg -1 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·kg -1 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·kg -1 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 TNF-αand IL-1β 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 TNF-α and IL-1β was demonstrated in blood samples from both groups. Serum TNF-α and IL-1β reached their peaks 3 h and 6 h after the injection of LPS and sodium taurocholate,respectively. The levels of serum TNF-α and IL-1β 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 TNF-α and IL-1β during inflammatory reactions in mice and rats and alleviate the acute lesions induced by inflammatory mediators.