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作 者:张宽顺 朱春胜[2] 石琳 ZHANG Kuanshun;ZHU Chunsheng;SHI Lin(Department of Hematology,the Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450046,China;The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
机构地区:[1]河南省中医院(河南中医药大学第二附属医院)血液科,河南郑州450046 [2]郑州大学第一附属医院,河南郑州450052
出 处:《现代药物与临床》2024年第11期2740-2745,共6页Drugs & Clinic
基 金:河南省医学科技攻关计划联合共建项目(LHGJ20190273)。
摘 要: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-αwere 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-αwere 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.
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