排酸护肾汤防治尿酸性肾病MAPK通路与尿酸相关靶点的研究

目的探讨排酸护肾汤对尿酸性肾病(uric acid nephropathy,UAN)大鼠治疗效果及其可能作用机制。方法随机且平均将80只雄性SD大鼠分成5组:正常组,模型组,排酸护肾组,别嘌呤醇组以及联合用药组。采用高酵母颗粒性饲料联合腺嘌呤灌胃,制造UAN模型。造模后第21天分别对肾匀浆中尿酸(uric acid,UA)、黄嘌呤氧化酶(xanthine oxidase,XOD)、肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen,BUN)水平进行检测;q-PCR法测定URAT1 mRNA表达;Western blot检测p38丝裂原活化蛋白激酶(p-p38MAPK)蛋白表达水平。结果中药排酸护肾汤可降低肌酐、尿素氮及黄嘌呤氧化酶水平,抑制尿酸转运体1(URAT1)的mRNA的表达,并下调p-p38MAPK蛋白的表达,抑制p38 MAPK信号通路的表达。结论排酸护肾汤主要通过降低Cr、BUN及XOD水平,抑制URAT1的mRNA的表达来促进尿酸的排泄,保护肾功能,并且通过作用于MAPK信号通路改善肾脏纤维化。

Study of MAPK Pathway and Uric Acid-related Target in Treatment of Uric Acid Nephropathy by Pai Suan Hu Shen Decoction

Objective To study the therapeutic effect and possible mechanism of uric acid nephropathy(UAN)in rats treated with paisuan hu shen decoction.Methods 80 SD male rats were randomly and averagely divided into 5 groups:the normal group,the model group,the pai suan hu shen group,the allopurinol group and the combined treatment group.UAN model was established by intragastric administration of high yeast pellet feed.On the 21st day after modeling,rats were sacrificed and the levels of renal homogenate uric acid(UA),xanthine oxidase(XOD),creatinine(Cr)and blood urea nitrogen(BUN)were determined.URAT1 mRNA expression was determined by q-PCR.Western blot was used to detect the expression level of p38 mitogen-activated protein kinase(p-p38mapk).Results Pai suan hu shen decoction can reduce the levels of creatinine,urea nitrogen and xanthine oxidase,inhibit the expression of URAT1 mRNA,down-regulating the expression function of p-p38mapk protein and inhibiting the expression of p38MAPK signaling pathway.Conclusion Pai suan hushen decoction can promote the excretion of uric acid and protect renal function by reducing the levels of Cr,BUN and XOD,and improving renal fibrosis by acting on MAPK signaling pathway.