Objective: To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF)β(1) in hyperuricemic rats. Methods: Forty male SD rats were divided into 4 groups: normal control group (NC group), oteracil potassium group (OP group), oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group). Each group had 10 rats and balanced in body weights. To induce hyperuricemia, rats were given oteracil potassium by gastric gavage once a day for eight weeks. Rats in OF group and OB group were given either febuxostat or benbromarone starting with oteracil potassium, and rats in NC group was given saline only. Blood samples were taken before, and at the end of 4 and 8 weeks of the treatments and serum uric acid, creatinine, blood usea nitrogen(BUN), IL-6 and TGFβ(1) contents were measured at each time point. Renal pathological changes were observed via HE and Masson staining, and the expression of α-SMA and E-cadherin were detected by immunohistochemistry. Results: Compared with those in NC group, the levels of serum uric acid, creatinine, BUN, IL-6 and TGFβ(1) in the another three groups were increased significantly (all P<0.01). However, the IL-6 and TGFβ(1) contents in OF group were much lower than those in OP group (P<0.01). HE and Masson staining showed that OF group had less damage and tubulointerstitial fibrosis than OP group and OB group (P<0.01). Moreover, the expression of α-SMA was significantly down-regulated (P<0.01) and that of E-cadherin was significantly up-regulated in OF group compared with those in OP group. Conclusion: Febuxostat treatment significantly inhibited EMT and reduced the levels of IL-6 and TGFβ(1) in hyperuricemia rats.
目的： 观察非布司他对高尿酸血症(HUA)大鼠肾小管上皮间质转化及血清IL－6、转化生长因子β(1)(TGF β(1))的影响。 方法： SD大鼠分为正常对照(NC)组、氧嗪酸钾(OP)组、氧嗪酸钾＋非布司他(OF)组和氧嗪酸钾＋苯溴马隆(OB)组，每组10只，各组大鼠体重均衡。OP灌胃建立HUA大鼠模型。检测大鼠血尿酸、肌酐(Scr)、尿素氮(BUN)，IL－6、TGFβ(1)的水平；HE及Masson染色观察肾组织病理变化情况，免疫组化法测定α－平滑肌肌动蛋白(α－SMA)、E钙黏蛋白(E－cadherin)表达。 结果： 与NC组比较，OP组、OF组和OB组血清尿酸、Scr、BUN、IL－6、TGFβ(1)水平均升高，差异有统计学意义(P<0.01)；第8周时，OF组IL－6、TGFβ(1)水平较OP组明显下降(P<0.01)；HE染色显示，OF组无明显炎症细胞浸润，肾小球及肾小管无明显损伤；Masson染色提示OP组肾纤维化程度大于其他3组(P<0.01)，OF组纤维化程度明显减轻；免疫组化检测发现，NC组肾组织不表达α－SMA，高表达E－cadherin；OF组与OP组比较α－SMA明显减少(P<0.01)，E－cadherin表达增加(P<0.01)。 结论： 非布司他能有效抑制尿酸性肾病肾小管表型转化；非布司他显著降低HUA大鼠血清IL－6及TGF－β(1)水平。.
Keywords: Epithelial-to-mysenchymal transition; Febuxostat; Hyperuricemia; Interleukin-6; Transforming growth factor beta1.