非布司他对高尿酸血症大鼠Treg/Th17平衡及血管内皮功能的影响

目的: 研究非布司他对高尿酸血症大鼠Treg/Th17平衡和血管内皮功能的影响。方法: 32只雄性SD大鼠随机分为4组,分别为正常对照组、模型组、非布司他组及别嘌醇组。模型组采用氧嗪酸钾联合酵母膏灌胃建立高尿酸血症模型,非布司他组和别嘌醇组在建立模型的同时分别给予非布司他（10 mg·kg-1·d-1）及别嘌醇（50 mg·kg-1·d-1）灌胃治疗6周。用ELISA法测定各组大鼠血清尿酸、白介素-6（IL-6）、一氧化氮（NO）及内皮素-1（ET-1）的含量,流式细胞术检测脾脏Treg及Th17细胞水平,HE及Masson染色观察主动脉内皮病理形态学变化。结果: 非布司他可显著降低高尿酸血症大鼠血清尿酸及IL-6含量,且疗效优于别嘌醇（P<0.05）。非布司他可上调高尿酸血症大鼠血清NO含量、下调ET-1含量（P<0.05）。流式细胞术结果显示非布司他可下调高尿酸血症大鼠Th17细胞水平,改善Treg/Th17平衡（P<0.05）。病理结果显示非布司他可改善内皮细胞肿胀、减少增生纤维组织和胶原纤维的沉积。结论: 非布司他可改善血管内皮功能障碍,其机制可能与其纠正Treg/Th17失衡有关。

Effects of febuxostat on Treg/Th17 balance and vascular endothelial function in rats with hyperuricemia

Objective: To investigate the effects of febuxostat on Treg/Th17 balance and vascular endothelial function in hyperuricemia rats. Methods: Thirty two male SD rats were randomly divided into 4 groups with 8 rats in each group, including normal control group, model group, febuxostat group and allopurinol group. Rats in model group and experimental group were given potassium oxazinate and yeast extract by gavage to establish a rat model of hyperuricemia. Febuxostat （10 mg·kg-1·d-1） and allopurinol （50 mg·kg-1·d-1） were given by gavage respectively to febuxostat group and allopurinol group for 6 weeks. After drug treatment, the levels of serum uric acid, interleukin-6 （IL-6）, nitric oxide （NO）, and endothelin-1 （ET-1） were measured by ELISA. The changes of Tregs and Th17 cells were measured by flow cytometry. HE and Masson staining were used to observe pathological changes of aortic endothelium tissues. Results: After febuxostat treatment, the levels of serum uric acid, IL-6 were significantly decreased （P<0.05）. The effects of febuxostat on reducing serum uric acid, IL-6 was better than that of allopurinol （P<0.05）. The levels of serum NO in the febuxostat group were higher than that in the model group （P<0.05）, while the levels of ET-1 were lower than that in the model group （P<0.05）. After febuxostat treatment, the percentages of Th17 cells were decreased while the ratios of Treg/Th17 were increased （P<0.05）. Histopathologic results showed that febuxostat could improve the swelling of endothelial cells and reduce the proliferation of fibrous tissue and deposition of collagen fibers. Conclusion: Febuxostat can improve vascular endothelial dysfunction in hyperuricemia rats, which may be related to its correction of Treg/Th17 imbalance. ［Key words］Febuxostat; hyperuricemia; Treg/Th17 balance; interleukin-6; nitric oxide; endothelin-1