氟比洛芬酯减轻肾缺血再灌注模型大鼠的炎症损伤研究

Study on Flurbiprofen Axetil Attenuates Inflammatory Injury in Renal Ischemia-reperfusion Model Rats

目的探索氟比洛芬酯(flurbiprofen axetil,FA)减轻大鼠肾缺血再灌注炎症损伤的生物学作用及其潜在的机制。方法将♂SD大鼠随机分为4组(每组8只):假手术组、假手术+FA(5 mg·kg^(−1))组、缺血再灌注损伤(ischemia-reperfusion injury,IRI)组和IRI+FA(5 mg·kg^(−1))组。分析血肌酐和尿素氮指标、进行肾脏组织学切片并进行病理学评分;免疫组织化学法检测肾脏凋亡指数,包括Bax和caspase-3和Bcl-2的水平;免疫组织化学法和蛋白质免疫印迹法检测纤维化指标,包括TGF-β1、Smad3和p-Smad3,以评估FA处理对肾IRI的影响。结果FA处理可显著抑制血清肌酸和血尿素氮水平的升高,同时改善IRI所致的组织学损害。此外,对于细胞凋亡信号通路,FA预处理可显著降低caspase-3和Bax的表达并增加Bcl-2的水平。对于纤维化信号通路,FA处理可下调典型纤维化分子(TGF-β1,Smad3,p-Smad3)的表达水平。结论FA处理对肾脏IRI具有保护作用,这可能与减轻炎症和纤维化水平有关。

OBJECTIVE To explore the biological effect and potential mechanism of flurbiprofen axetil(FA)on attenuating renal ischemia-reperfusion inflammation injury in rats.METHODS Male SD rats were randomly divided into 4 groups(8 in each group):sham operation group,sham operation+FA(5 mg·kg^(−1))group,ischemia-reperfusion injury(IRI)group and IRI+FA(5 mg·kg^(−1))group.To analysis serum creatinine and urea nitrogen index,renal histological section and pathological score were performed;immunohistochemical method was used for detecting renal apoptosis indexes,including Bax and caspase-3 and Bcl-2 levels;immunohistochemistry and Western blotting methods for the detection of fibrosis,including TGF-β1,Smad3,and p-Smad3,so as to evaluate the effect of FA treatment on renal IRI.RESULTS FA treatment significantly inhibited serum creatine and blood urea nitrogen levels and improved histological damage caused by IRI.In addition,FA pre-treatment significantly reduced the expression of caspase-3 and Bax and increased the level of Bcl-2 for the apoptotic signaling pathway.For fibrotic signaling pathways,FA treatment could down-regulate the expression levels of typical fibrotic molecules(TGF-β1,Smad3,p-Smad3).CONCLUSION FA has protective effect on renal IRI,which may be related to the reduction of inflammation and fibrosis levels.