菊苣提取物和非布司他联用降尿酸作用研究

doi:10.19803/j.1672-8629.20250344

摘要/Abstract

摘要： 目的选用菊苣提取物和非布司他作为中西药联用示例探究二者联用对高尿酸血症（HUA）大鼠的药效作用并进行安全性评估,为二者联用降尿酸提出警戒思考。方法 SD大鼠随机分为对照组、HUA模型组、非布司他低剂量组（0.9 mg·kg^-1,以下简称“非低组”）、非布司他高剂量组（1.8 mg·kg^-1,以下简称“非高组”）、菊苣提取物低剂量（2.5 g·kg^-1,以下简称“菊苣低组”）、菊苣提取物高剂量组（5.0 g·kg^-1,以下简称“菊苣高组”）、非低+菊苣低组、非低+菊苣高组、非高+菊苣低组和非高+菊苣高组,共10组。以氧嗪酸钾（750 mg·kg^-1）联合酵母提取物浸膏（10 g·kg^-1）建立HUA大鼠模型,连续灌胃28 d,动态检测各组大鼠血清尿酸（SUA）水平,实验结束后,检测大鼠血清中黄嘌呤氧化酶（XOD）水平及心脏、肝脏、肾脏相关指标水平和组织病理情况,对其安全性进行评估,提出菊苣提取物和非布司他联用降尿酸的警戒思考。结果实验各阶段,HUA状态下4个联用药组大鼠SUA水平均显著降低,此外各联用组降尿酸强度均高于对应剂量下的单用药组,28 d的非布司他高剂量+菊苣高剂量组降尿酸强度显著高于非布司他高剂量组及菊苣高剂量组（P<0.05）。心、肝、肾的安全指标和组织病理染色结果显示4个联用组与对照组相比无明显改变,说明联用降尿酸具有良好的安全性,且与非布司他单药组（尤其高剂量）相比,联用组心肾损伤指标显著改善。此外非布司他低剂量组联用菊苣提取物,在保证良好降尿酸效果的同时,安全性优于联用非布司他高剂量组。结论菊苣提取物联用非布司他可显著降低血尿酸水平,效果优于对应剂量下单用药且安全性高,且非布司他低剂量联用整体效果更佳,建议从临床最低剂量开始使用,定期监测血尿酸水平及脏器功能,关注药物相互作用等,保障患者安全用药。

关键词: 菊苣提取物, 非布司他, 中西药联用, 降尿酸, 高尿酸血症, 药物警戒, 大鼠

Abstract: Objective To explore the efficacy and safety of the combination of chicory extract and febuxostat in treating hyperuricemia in rats, and to give tips about related pharmacovigilance. Methods SD rats were randomly divided into ten groups including the control group, HUA model group, low and high-dose febuxostat groups (0.9 mg·kg^-1 and 1.8 mg·kg^-1), low and high-dose chicory extract groups (2.5 g·kg^-1 and 5 g·kg^-1), low-dose febuxostat+low-dose chicory extract group, low-dose febuxostat + high-dose chicory extract group, high-dose febuxostat + low-dose chicory extract group, and the high-dose febuxostat + high-dose chicory extract group. A hyperuricemia rat model was established via 28 consecutive days of intragastric administration of potassium oxonate (750 mg·kg^-1) and yeast extract (10 g·kg^-1). The levels of serum uric acid (SUA) in each group were dynamically monitored. After the experiment, the serum levels of xanthine oxidase (XOD), related indicators and histopathological conditions of the heart, liver, and kidneys were detected to evaluate the safety of the combination. Considerations for the combined use of chicory extract and febuxostat in reducing uric acid were outlined. Results At each stage of the experiment, the SUA levels of rats in the four combination groups under the hyperuricemia state were significantly reduced. Levels of uric acid were lowered more significantly in each combination group than that in the single-agent groups at the corresponding dose, and more markedly in the febuxostat high-dose + chicory high-dose group at 28 d than in the febuxostat high-dose group and chicory high-dose group (P<0.05). The safety indexes of the heart, liver and kidney and results of histopathological staining pointed to no significant changes in the four combination groups compared with the control group, suggesting that the combination could be safely used for lowering uric acid. The indexes of the heart and kidney injury were more significantly improved in the combination group than in the febuxostat single-dose group (especially the high dose). In addition, the combination of chicory extract with febuxostat in the low-dose group had a better safety profile than the combination in the high-dose group. Conclusion The combination of chicory extract and febuxostat can significantly reduce serum levels of uric acid, with better efficacy and safety than single use. The overall effect is the best in the low-dose febuxostat combined with chicory extract group. It is recommended that clinicians start with the minimum dose, regularly monitor serum uric acid levels and organ functions, and be wary of drug interactions.

Key words: Chicory Extract, Febuxostat, Combination of Traditional Chinese and Western Medicine, Lowering of Uric Acid, Hyperuricemia(HUA), Pharmacovigilance, Rat

中图分类号:

王雪, 张晓朦, 张冰, 林志健. 菊苣提取物和非布司他联用降尿酸作用研究[J]. 中国药物警戒, 2025, 22(11): 1201-1210.

WANG Xue, ZHANG Xiaomeng, ZHANG Bing, LIN Zhijian. Combined Hypouricemic Effect of Chicory Extract and Febuxostat: an Example of Synergistic Effect of Traditional Chinese Medicine and Western Medicine[J]. Chinese Journal of Pharmacovigilance, 2025, 22(11): 1201-1210.

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