目的 探讨药芹二糖苷A治疗高尿酸血症小鼠的药效机制。方法 采用氧嗪酸钾与腺嘌呤诱导高尿酸血症小鼠模型，小鼠随机分为对照组、模型组、苯溴马隆组、药芹二糖苷A（10、20 mg/kg）组。检测小鼠血清尿酸（UA）、尿素氮（BUN）、肌酐（CRE）、白细胞介素1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平，苏木素–伊红（HE）染色观察药芹二糖苷A对小鼠肾脏病理的影响，蛋白免疫印迹法检测肾脏核心蛋白的表达。结果 与模型组比较，药芹二糖苷A可显著降低模型小鼠血清UA、BUN、CRE，减少炎症因子IL-1β、IL-6、TNF-α水平（P＜0.05、0.01）；HE显示药芹二糖苷A可改善肾脏囊腔水肿和肾小管萎缩，减小肾小球体积；Western blotting显示药芹二糖苷A可显著升高肾脏有机阴离子转运体3（OAT3）蛋白表达量，降低葡萄糖转运体9（GLUT9）和尿酸盐阴离子转运体（URAT1）蛋白表达量（P＜0.01）。结论 药芹二糖苷A发挥治疗高尿酸血症的机制可能与改善肾功能，降低炎症因子的释放及调控肾脏OAT3、GLUT9和URAT1蛋白表达有关。

Objective To investigate the therapeutic mechanism of graveobioside A in treatment of hyperuricemia. Methods Potassium oxonate and adenine were used to induce hyperuricemia mouse model. The mice were randomly divided into control group, model group, benbromarone group, and graveobioside A (10, 20 mg/kg) group. The levels of serum UA, BUN, CRE, IL-1β, IL-6, and TNF-α were detected. The effects of graveobioside A on renal pathology in mice were observed by HE staining. The expression of renal core protein was detected by Western blotting. Results Compared with model group, CRE, UA, BUN, and CRE in serum of graveobioside A group were significantly decreased, and the levels of inflammatory cytokines IL-1β, IL-6 and TNF-α were decreased (P < 0.05, 0.01). HE showed that graveobioside A could improve renal cystic edema and renal tubule atrophy, and reduce glomerular volume. Western blotting showed that graveobioside A significantly increased the expression of OAT3 protein in kidney, and decreased the expression of GLUT9 and URAT1 protein (P < 0.01). Conclusions The mechanism of graveobioside A in treatment of hyperuricemia may be related to improving renal function, reducing the release of inflammatory factors, and regulating the expression of kidney OAT3, GLUT9 and URAT1 proteins.

R285.5

河南省医学科技攻关计划联合共建项目(LHGJ20190273)