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

关键词:  氟比洛芬酯  缺血再灌注  肾脏  炎症  纤维化

Key words:  flurbiprofen axetil  ischemia-reperfusion  kidney  inflammation  fibrosis

摘要:

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。

Abstract:

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.