基于“肠-肾”途径的健脾祛湿中药抗痛风病研究

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

目的:从“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。

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.