王雨 褚梦真 李文静 林志健 张冰

摘要 目的：從“肠-肾”途径探讨健脾祛湿中药防治痛风病作用。方法：10%果糖塑造大鼠高血尿酸模型，高钙高嘌呤食饵并限水诱导鹌鹑尿酸盐沉积模型，以菊苣、参苓白术散为示例药。生化检测大鼠血清尿酸（SUA）、粪便尿酸（FUA）水平，计算肾脏尿酸清除率（RCUA）;检测鹌鹑粪尿中尿酸含量，计算尿酸排泄量。免疫组化分析大鼠肠道ABCG2、肾脏URAT1、OAT1，及鹌鹑肠道Occludin、肾脏p-p65表达。六胺银染色分析尿酸盐沉积。结果：1）菊苣可显著降低模型大鼠SUA、增加FUA、RCUA，促进肠道ABCG2表达，减少肾脏URAT1表达。2）参苓白术散可显著减少模型鹌鹑肾脏尿酸盐沉积，增加尿酸排泄量，增加肠道Occludin表达，减少肾脏p-p65表达。结论：痛风病发生发展中存在“肠-肾”途径的病理改变，健脾祛湿中药通过调节“肠-肾”尿酸转运促尿酸排泄、改善肠道屏障功能及肾脏炎症状态以祛除尿酸盐沉积，共同发挥防治痛风病作用。

关键词 “肠-肾”途径;健脾祛湿中药;痛风病;高血尿酸;尿酸盐沉积

Study on Anti-gout Disease of Traditional Chinese Medicines for Invigorating Spleen and Removing Dampness Based on Intestine and Kidney Axis

WANG Yu，CHU Mengzhen，LI Wenjing，LIN Zhijian，ZHANG Bing

（School of Chinese Materia Medica，Beijing University of Chinese Medicine，Beijing 102488，China）

Abstract Objective：From the “intestine-kidney” axis to explore the anti-gout disease effect of traditional Chinese medicine for invigorating spleen and removing dampness.Methods：10% fructose created a rat model of high blood uric acid，a high-calcium，high-purine diet and water restriction induced quail urate deposition model，with Cichorium intybus L.and Shenlingbaizhu Powder as example drugs.Biochemical detection of rat serum uric acid（SUA）and fecal uric acid（FUA）levels were detected.The renal uric acid clearance（RCUA）was calculated; uric acid content in quail feces and urine were detected; uric acid excretion was calculated.Rat intestine ABCG2，kidney URAT1，OAT1，quail intestine Occludin，and kidney p-p65 expression were analyzed by Immunohistochemistry.Hexamine silver staining was used to analyze urate deposition.Results：1）Cichorium intybus L.could significantly reduce SUA level，increase FUA and RCUA levels of model rats，increase expression of intestinal ABCG2 and decrease expression of renal URAT1.2）Shenling Baizhu Powder could significantly reduce the renal urate deposition in quails，increase the excretion of uric acid，as well as raise expressions of intestinal Occludin and decrease expressions of renal p-p65.Conclusion：There are some pathological changes of ‘intestine-kidney axis in the development of gout disease.Traditional Chinese medicine for invigorating spleen and removing dampness could prevent and treat the gout disease by adjusting the urate transporters in the intestine and kidney to promote excretion of uric acid，and improving the intestinal barriers and renal inflammatory state to remove the urate deposition.

Keywords Intestine and kidney axis; Traditional Chinese medicine for invigorating spleen and removing dampness; Gout disease; Hyperuricemia; Urate deposition

中图分类号：R242;R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.01.003

痛风病是指与高尿酸血症、尿酸盐沉积密切相关的进展性代谢性疾病，2020年《高尿酸血症/痛风患者实践指南》根据临床疾病状态，将痛风病理进展分为了3个阶段、8个状态[1]，其中高血尿酸是痛风病发生的重要生化基础，尿酸盐沉积是诱发痛风病急性炎性反应的重要因素。由此提示，降低高血尿酸、减少尿酸盐沉积将有助于抑制痛风病的发生发展。中医学理论认为尿酸代谢异常引起的高血尿酸及其沉积属于“湿邪”“浊滞”范畴，临床常切入脾胃肠肾等器官以健脾化湿泄浊，取得了较好的疗效[2]，本组前期也发现健脾祛湿药物对实验性高血尿酸亦有显著的降低作用[3-4]。……