藏药二十五味儿茶丸降尿酸作用及对尿酸转运蛋白表达水平的影响

Hypouricemic effects of Tibetan medicine Ershiwuwei Ercha Pills and influences on the expressions of uric acid transporters

目的研究藏药二十五味儿茶丸对氧嗪酸钾联合次黄嘌呤诱导的大鼠高尿酸血症的防治作用。方法 60只大鼠随机分为空白组、模型组、别嘌醇组(10 mg/kg)和二十五味儿茶丸高、中、低剂量组(1、0. 5、0. 25 g/kg),除空白组外,其余各组皮下注射氧嗪酸钾(200 mg/kg)联合灌胃次黄嘌呤(300 mg/kg)建立高尿酸血症模型,1 h后灌胃给予相应药物,连续7 d。生化法测定血清尿酸(UA)、肌酐(Cr)、尿素氮(BUN)水平,血清及肝组织中黄嘌呤氧化酶(XOD)活性; HE染色观察肾脏组织病理变化;免疫组化法测定肾脏有机阴离子转运蛋白1 (OAT1)、有机阴离子转运蛋白3 (OAT3)及尿酸盐阴离子转运体1 (URAT1)的表达。结果与空白组比较,模型组血尿酸水平、血清及肝脏组织XOD水平显著升高,肾脏组织出现病理损伤,肾脏组织OAT1及OAT3表达显著降低,URAT1表达显著升高。与模型组比较,二十五味儿茶丸高剂量组能明显降低血尿酸水平,抑制XOD活性,改善肾脏病理损伤,升高OAT1及OAT3的表达,抑制URAT1的表达。结论二十五味儿茶丸可以有效治疗高尿酸血症并对肾脏有一定的保护作用,其降尿酸机制可能与抑制XOD活性,提高OAT1、OAT3的表达,抑制URAT1的表达有关。

AIM To study the preventive and therapeutic effects of TilDetan medicine Ersliiwuwei Ercha Pills on hyperuricemia induced by oteracil potassium and xanthoglobulin in rats.METHODS Sixty male rats randomly divided into blank group,model group,allopurinol group(10 mg/kg)and Ershiwuwei Ercha Pills high-dose,medium-dose,low-dose groups(1,0.5,0.25 g/kg)were subcutaneously injected with oteracil potassium(200 mgkg)and xanthoglobulin gavage(300 m/kg)to establish hyperuricemia model(except for the blank group),1 h after which subsequent seven-day intragastrical medications started.Uric acid(UA),creatinine(Cr),urea nitrogen(BUN)levels in serum,xanthine oxidase(X0D)activities in serum and liver tissue were detected by biochemistry method.HEstaining was used to observe the pathological changes of kidney tissues.The renal expressions of organic anion transporters 1(0AT1),organic anion transporters 3(0AT3),urate anion transporter 1(URAT1)were determined by immunohistochemistry.RESULTS Compared with the blank group#the model group demonstrated significant rise in blood level of uric acid elevation of serum and tissue XOD levels the kidney impairment was revealed by remarlkable kidney OAT1 and OAT3 expressions reduction and URAT1 ex-pression increase as well.The Ersliiwuwei Ercha Pills high-dose group showed its superiority to the model group in terms of significant blood uric acid level reduction XOD activity inhibition expression increase of OAT1 and OAT3 and expression inhibition of URAT1.CONCLUSION The mechanism of Ersliiwuwei Ercha Pills as an antihyperuricemic medication and an enhancer of renal function may be associated with its capacity in inhibitingXOD activity,upregulating the expressions of renal OAT1 OAT3 and decreasing the expression of renal URAT1.