复方芪苓配方颗粒治疗大鼠高尿酸血症的作用机制研究

Study on Mechanism of Compound Qiling Formula Granules in Treatment of Hyperuricemia in Rats

关键词:  复方芪苓配方颗粒  高尿酸血症  肾脏转运体

Key words:  Compound Qiling Formula granules  hyperuricemia  kidney transporter

摘要:

目的 研究复方芪苓配方颗粒对高尿酸血症大鼠的降尿酸作用，并从尿酸排泄途径探讨其作用机制。方法 SD大鼠随机分为正常组、模型组、苯溴马隆组、复方芪苓配方颗粒高、中、低剂量组（9.6，4.8，2.4 g·kg^-1），通过腺嘌呤灌胃及氧嗪酸钾皮下注射建立高尿酸血症模型，连续给药14 d。分别测定血清尿酸、肌酐、尿素、尿尿酸水平，计算肾脏尿酸清除率。采用RT-PCR分别测定动物肾脏中相关转运体的表达水平；观察肾组织病理改变。结果 与模型组比较，复方芪苓配方颗粒组高尿酸血症大鼠的血清尿酸、肌酐、尿素水平显著降低，其肾脏尿酸清除率显著升高；其肾组织病理改变显示，肾小管内尿酸盐结晶减少，肾小管-间质损伤较轻。复方芪苓配方颗粒可以显著下调肾脏尿酸盐转运体1、葡萄糖转运蛋白9 mRNA的表达，上调有机阴离子转运体1 mRNA的表达。结论 复方芪苓配方颗粒能降低高尿酸血症大鼠的血清尿酸水平并减轻肾组织病理损害，其作用机制可能是通过调节尿酸转运体的表达水平，以降低肾脏尿酸盐重吸收能力、增加尿酸盐分泌，从而促进尿酸排泄。

Abstract:

OBJECTIVE To investigate the effect of Compound Qiling Formula granules in treatment of hyperuricemia in rats, and to explore its mechanism from the excretion pathway of uric acid. METHODS The SD rats were randomly divided into normal group, model group, benzbromarone group and high, medium and low dose group of Compound Qiling Formula granules(9.6, 4.8, 2.4 g·kg^-1). Establish the hyperuricemia model by adenine gavage and subcutaneous injection of potassium oxalate for 14 consecutive days. The levels of serum uric acid, creatinine, urea and urine uric acid were tested respectively, the clearance rates of uric acid in kidney were calculated. The expression of related transporters in kidney of animals was measured by RT-PCR. The pathological changes in kidney were observed. RESULTS Compared with model group, the levels of serum uric acid, creatinine and urea of the hyperuricemia rats in Compound Qiling Formula granules groups were significantly reduced, the clearance rates of uric acid in kidney were significantly increased; their pathological changes of kidney tissue showed that they had less urate crystals of renal tubules and less renal tubule-interstitial damage. Compound Qiling Formula granules could significantly down-regulate the mRNA expression of uric acid transporter 1, glucose transporter 9 and up-regulate the mRNA expression of organic anion transporter 1. CONCLUSION Compound Qiling Formula granules can reduce uric acid level and alleviate renal pathological damage in rats with hyperuricemia. Its mechanism of action may be related to the regulation of the expression level of uric acid transporters, so as to reduce the reabsorption capacity of renal uric acid salt, increase the secretion of uric acid salt, thus promoting the excretion of uric acid.