大车前苷对氧嗪酸钾诱导小鼠急性高尿酸血症模型的影响

Effect of plantamajoside on acute hyperuricemia model induced by potassium oxonate in mice

目的研究大车前苷(plantamajoside,PMS)对氧嗪酸钾盐(postassium oxonate,OA)诱导急性高尿酸血症模型小鼠的影响及其作用机制。方法选取60只小鼠,随机均分为正常组,模型组,阳性组,PMS低、中、高剂量组。腹腔注射OA造成实验所需模型,连续灌胃给药7 d,于造模完毕1 h之后各组小鼠眼眶采血、取肝脏及肾脏,测定血清中尿酸等生化指标含量,通过Western blot检测小鼠肾组织有机阴离子转运体(OAT1)等蛋白表达水平。结果与正常组相比,模型组小鼠血清中尿酸等生化指标含量及肝脏中黄嘌呤氧化酶水平明显升高,小鼠肝脏中TLR4、NLRP3等蛋白表达水平明显升高、尿酸转运体GLUT9、URAT1水平明显上调、OAT1水平明显下调;与模型组相比,PMS能明显下调小鼠血清中尿酸等生化指标含量以及肝脏中TLR4、NLRP3等蛋白表达水平、肾脏中GLUT9蛋白表达水平,并明显升高OAT1蛋白表达水平,病理切片显示PMS能改善小鼠肾组织病变。结论PMS对急性高尿酸血症小鼠存在一定保护作用,其作用机制和肾脏尿酸转运体、TLR/MyD88/NF-κB及NLRP3炎症通路有关。

Aim To study the effect of plantamajoside on acute hyperuricemia model mice induced by potassium oxazinate and its mechanism.Methods Sixty mice were randomly divided into normal group,model group,positive group and plantamajoside low,medium and high dose groups.The model was established by intraperitoneal injection of potassium oxazinate,which was administered by gavage for 7 days.After 1 hour,blood was collected from the eyes,liver and kidney of mice in each group,and the contents of biochemicalindexes such as uric acid in serum were measured.The expression level of protein such as organic anion transporter(OAT1)in kidney tissues of mice was detected by Western blot.Results Compared with normal group,the content of biochemical indexes such as uric acid in serum and xanthine oxidase in liver of model group mice significantly increased,the expression levels of TLR4,NLRP3 and other proteins in liver of mice significantly increased,the levels of uric acid transporters GLUT9 and URAT1 significantly increased,and the level of OAT1 significantly decreased.Compared with model group,plantamajoside could significantly down-regulate biochemical indexes such as uric acid in serum,TLR4,NLRP3 protein expression in liver,GLUT9 protein expression in kidney,and significantly increase OAT1 protein expression level.Pathological section showed that plantamajoside could improve kidney pathological changes in mice.Conclusions Plantamajoside has certain protective effect on acute hyperuricemia mice,and its mechanism is related to renal uric acid transporter,TLR/MyD88/NF-κB and NLRP3 inflammatory pathway.