己酮可可碱对非酒精性脂肪性肝炎大鼠肝NF-κB活性作用的研究

THE EFFECT OF PENTOXIFYLLINE ON HEPATIC NF-κB ACTIVITY OF NONALCOHOLIC STEATOHEPATITIS IN RATS

目的探讨己酮可可碱(PTX)对非酒精性脂肪性肝炎(NASH)大鼠肝核因子-κB(NF-κB)蛋白的活性作用。方法SD大鼠40只,标准饲料喂养1周后,随机分为4组:对照组、12周模型组、16周模型组和PTX治疗组。用高脂饮食法建立大鼠非酒精性脂肪性肝炎模型,采用免疫组织化学染色法检测大鼠肝组织NF-κB和κB抑制蛋白α(IκB-α)的表达,应用Western blotting的方法检测肝组织中NF-κB的表达。结果免疫组织化学及Westernblotting结果表明,与对照组相比,模型组及PTX治疗组大鼠肝NF-κB的表达显著增加(P<0.05),IκB-α显著降低(P<0.05)。与16周模型组相比,PTX治疗组NF-κB的表达有所降低,IκB-α有显著提高(P<0.05)。结论PTX能抑制大鼠肝IκB的降解,减少NF-κB的活化。

Objective To investigate the effect of pentoxifylline on hepatic NF-κB activity of nonalcoholic steatohepatitis （NASH） in rats. Methods Rats fed with a standard diet for one week were randomly divided into four groups： the control group （ n = 10）, the 12-week-model group（ n = 10）, the 16-week-model group（ n = 10） and the PTX treatment group（ n = 10）. Two model groups and the PTX treatment group were fed with a high-fat diet and the control group with a standard diet. After 12 week, the 12-week-model group were sacrificed and the treatment group were given PTX [ 16mg/（ kg· d）] by intragastric administration. Then all the remaining rats were sacrificed at the end of the 16th week. The expressions of NF-κB and inhibitor κB-α（IκB-α） proteins in livers were analyzed by immunohistochemistry. The expression of NF-κBp65 protein was determined by Western blotting. Results The expression of NF-κBp65 increased significantly in the model groups and the PTX treatment group （vs the control group, P 〈 0.05） but decreased in the PTX treatment group （vs the model groups）; the expression of IκB markedly decreased in the model groups and the PTX treatment group （vs the control group, P 〈 0.05） and increased in the PTX treatment group （vs the model groups, P 〈 0.05）. Conclusion PTX can inhibit the degradation of IκB protein in rat livers and decrease the activity of NF-κB.