橄榄果汁冻干粉的降尿酸与抗痛风作用

Anti-hyperuricemic and Anti-gout Effects of Olive Juice Freeze Dried Powder in Rats

采用高尿酸血症大鼠与痛风性关节炎大鼠模型,考察橄榄果汁冻干粉(Hidrox;12%)的降尿酸与抗痛风作用及机制。通过腹腔注射氧嗪酸钾(Potassium oxazinate,PO)建立高尿酸血症大鼠动物模型,灌胃相应药物,检测血清尿酸(Uric Acid,UA)、肌酐(Creatinine,CR)、尿素氮(Blood Urea Nitrogen,BUN)含量和血清与肝脏黄嘌呤氧化酶(Xanthine Oxidase, XOD)活性水平,检测肾皮质尿酸转运蛋白1(Recombinant Urate Transporter 1,URAT1)表达水平。通过给大鼠踝关节腔注射尿酸钠晶体(Monosodium Urate,MSU)建立痛风性关节炎大鼠模型,评价橄榄果汁冻干粉对痛风性关节炎大鼠关节肿胀、血清肿瘤坏死因子α(Tumor Necrosis Factor-α,TNF-α)与白细胞介素1β(Interleukin-1β,IL-1β)水平的影响。通过UPLC-ESI-MS/MS法分离与鉴定降尿酸的有效成分。结果显示,与模型组相比,橄榄果汁冻干粉(80 mg/kg)能极显著降低大鼠血清尿酸水平(P<0.01),极显著改善高尿酸导致的血清CR与BUN升高(P<0.01)。橄榄果汁冻干粉降尿酸的机制可能与其降低血清和肝脏XOD活性、下调URAT1表达等有关。在痛风性关节炎模型中,橄榄果汁冻干粉(80 mg/kg)能高度显著改善MSU导致的关节肿胀(P<0.001),显著降低血清TNF-α与IL-1β水平(P<0.05)。进一步研究发现,橄榄果汁冻干粉成分中胡椒碱与木犀草素能有效抑制HEK-293T细胞URAT1的尿酸转运,可能是其降尿酸的活性成分。综上,橄榄果汁冻干粉能有效降低腹腔注射PO导致的高尿酸血症大鼠的尿酸水平,改善大鼠踝关节注射MSU晶体引起的痛风关节炎症状,其机制可能是降低肝脏XOD活性、下调URAT1表达以及改善炎症水平。

To investigate the anti-hyperuricemic and anti-gout effects of olive juice freeze dried powder(Hidrox;12%) and its underlying mechanisms, a hyperuricemia rat model was established by intraperitoneal injection of potassium oxazinate and was given olive juice freeze dried powder administration. The levels of serum uric acid(UA), creatinine(CR) and urea nitrogen(BUN), serum and hepatic xanthine oxidase(XOD) activities, and the protein expression level of urate transporter1(URAT1) in kidney were evaluated. Besides, a gout rat model induced by monosodium urate(MSU) was established to detect the effects of olive juice freeze dried powder on the paw swelling rate, and the level of TNF-α and IL-1β in serum.UPLC-ESI-MS/MS method was used to separate and identify the active ingredients for lowering UA. Results showed that,when compared with the model group, olive juice freeze dried powder(80 mg/kg) could significantly reduce the serum UA level(P<0.01) and reverse the elevated serum CR and BUN(P<0.01) levels caused by hyperuricemia. Further study revealed that the anti-hyperuricemic effect of olive juice freeze dried powder might be associated with its inhibition toward the serum and hepatic XOD activities and the downregulation of renal URAT1 expression. In the gouty model, olive juice freeze dried powder(80 mg/kg) significantly alleviated the joint swelling(P<0.001) caused by MSU and reduced the serum TNF-α and IL-1β levels respectively(P<0.05). Further study revealed that piperine and luteolin might be the active ingredients of olive juice freeze dried powder owing to their inhibitory activity on URAT1-mediated urate transport in vitro. In summary, olive juice freeze dried powder could alleviate hyperuricemia and acute gouty arthritis in vivo, the uric acid-lowering effect of which might be related to the inhibition of XOD activities and down-regulation of renal URAT1 expression as well as inhibiting inflammatory reactions.