水蛭素抗痛风作用及其机制研究

Anti-gout effect of hirudin and its mechanism

目的探讨水蛭素抗痛风作用及其机制。方法利用次黄嘌呤复制小鼠高尿酸血症模型,尿酸钠诱导大鼠急性痛风性炎症模型,观察水蛭素对急性高尿酸血症尿酸水平及其诱导炎症的影响;利用氧嗪酸钾诱导小鼠慢性高尿酸血症模型,观察水蛭素对慢性高尿酸血症小鼠血清尿酸、尿素氮水平及血清、肝脏黄嘌呤氧化酶活性,肾脏的病理学改变、C-反应蛋白(CRP)水平及葡萄糖转运体9(GLUT9)表达的影响。结果水蛭素可显著降低次黄嘌呤引起的高尿酸血症小鼠血清尿酸水平,显著抑制由尿酸钠引起的大鼠足跖急性肿胀;可显著降低由氧嗪酸钾引起的慢性高尿酸小鼠血清高尿酸水平,降低血清尿素氮水平,显著抑制GLUT9的表达,减轻肾脏病理学损伤。结论水蛭素具有显著的抗高尿酸血症及抗痛风作用,其机制可能与保护肾脏作用及调节GLUT9表达有关。

Objective To investigate the anti-gout effect of hirudin and its mechanism. Methods Hypoxanthine was used to replicate mouse model of hyperuricemia. Sodium uric induced acute gouty inflammation in rats to observe the effect of hirudin on the level of uric acid and inflammation induced by acute hyperuricemia. The serum uric acid, serum urea nitrogen, serum xanthine oxidase activity, and liver xanthine oxidase activity were observed in chronic hyperuricemia mouse model induced by potassium oxonate. The changes of renal pathology, the level of C-reactive protein（CRP） and the expression of glucose transporter 9（GLUT9） were also be tested. Results Hirudin could significantly reduce the serum uric acid level in hyperuricemia mice induced by hypoxanthine and significantly inhibit acute toe swelling induced by sodium uric acid in rats. It could significantly reduce the level of serum hyperuricemia, decrease the level of blood urea nitrogen（BUN）, significantly inhibit the expression of GLUT9 and alleviate the pathological changes of kidney in chronic hyperuricemia mice induced by potassium oxazinate. Conclusion Hirudin has significant anti-hyperuricemia and anti-gout effects, and its mechanism may be related to the protection of kidney and the regulation of GLUT9 expression.