黄腐酚对高尿酸血症大鼠血尿酸水平及骨代谢的调控作用  

Regulation of xanthohumol on serum uric acid level and bone metabolism in hyperuricemia rats

作　　者：韩健勇 夏天爽 蒋益萍 范围晴 李琨 赵志新 辛海量 HAN Jianyong;XIA Tianshuang;JIANG Yiping;FAN Weiqing;LI Kun;ZHAO Zhixin;XIN Hailiang(Department of Pharmacognosy,School of Pharmacy,Naval Medical University(Second Military Medical University),Shanghai 200433,China;Department of Pharmacy,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Department of Pharmacy,Hongkou Branch of The First Affiliated Hospital of Naval Medical University(Second Military Medical University),Shanghai 200081,China)

机构地区：[1]海军军医大学(第二军医大学)药学系生药学教研室,上海200433 [2]上海中医药大学附属岳阳中西医结合医院药学部,上海200437 [3]海军军医大学(第二军医大学)第一附属医院虹口院区药剂科,上海200081

出　　处：《海军军医大学学报》2024年第3期260-267,共8页Academic Journal of Naval Medical University

基　　金：国家自然科学基金(82174079);上海市科学技术委员会生物医药领域科技支撑项目(21S21902600)。

摘　　要：目的考察黄腐酚(XAN)对高尿酸血症(HUA)大鼠的降血尿酸(UA)及调控骨代谢活性作用。方法将48只雄性Wistar大鼠随机分为6组(n=8):空白组,模型组,别嘌醇(ALLO)组,黄腐酚低剂量(XAN-L)组、中剂量(XAN-M)组、高剂量(XAN-H)组。采用氧嗪酸钾(200 mg·kg^(-1)·d^(-1))与次黄嘌呤(250 mg·kg^(-1)·d^(-1))联用法建立HUA模型。造模2 h后,各药物组分别给予相应药物混悬液(ALLO 20 mg·kg^(-1)·d^(-1),XAN5 mg·kg^(-1)·d^(-1),XAN 15 mg·kg^(-1)·d^(-1),XAN 45 mg·kg^(-1)·d^(-1)),灌胃干预14 d。分别于第3、7、10、14天进行眼眶取血,检测血清中UA、肌酐(CRE)、尿素氮(BUN)水平及黄嘌呤氧化酶(XOD)活性。实验结束测定碱性磷酸酶(ALP)活性,以及骨代谢相关蛋白Runt相关转录因子2(Runx2)、组织蛋白酶K(CTSK)、核因子κB受体活化因子配体(RANKL)和护骨因子(OPG)水平,并对RANKL/OPG比值进行分析。结果与空白组相比,第3、7、10、14天模型组大鼠血清UA水平升高(均P<0.01),表明大鼠HUA模型成功构建。与模型组相比,XAN-M、XAN-H可有效降低急、慢性HUA大鼠血清UA水平(均P<0.01)、抑制XOD活性(均P<0.01)、改善肾功能指标CRE(均P<0.01)和BUN(均P<0.05)。XAN-L虽未明显降低急性HUA大鼠的血清UA水平,但可有效降低XOD活性(P<0.01),并改善其肾功能指标CRE(P<0.01)和BUN(P<0.05);而对于慢性HUA大鼠,其能够有效降低血清UA水平(均P<0.01),却无明显肾保护作用。各剂量组XAN还可不同程度增强HUA大鼠的ALP活性(均P<0.01)、上调Runx2表达(XAN-L组除外,均P<0.01)、下调CTSK的表达(均P<0.01)、抑制RANKL分泌(均P<0.01)、促进OPG的表达(仅XAN-H组,P<0.01)、纠正RANKL/OPG的比值(均P<0.05)。结论XAN具有降低HUA大鼠血UA水平的作用,这可能与其抑制XOD活性以减少UA生成及保护肾功能以加强UA排泄有关;XAN还具有促进骨形成、抑制骨破坏,有效调控骨代谢的作用,这可能与其通过RANKL/OPG信号通路抑制破骨细胞分化�Objective To investigate the effects of xanthohumol(XAN)on reducing serum uric acid(UA)and regulating bone metabolism in hyperuricemia(HUA)rats.Methods Totally 48 male Wistar rats were randomly divided into 6 groups(n=8):blank group,model group,allopurinol(ALLO)group,XAN low-dose(XAN-L)group,XAN medium-dose(XAN-M)group,and XAN high-dose(XAN-H)group.The HUA model was developed by the combined use of potassium oxonate(200 mg·kg^(-1)·d^(-1))and hypoxanthine(250 mg·kg^(-1)·d^(-1)).After HUA model was established for 2 h,corresponding concentrations of drug suspension(20 mg·kg^(-1)·d^(-1) in ALLO group,5 mg·kg^(-1)·d^(-1) in XAN-L group,15 mg·kg^(-1)·d^(-1) in XAN-M group,and 45 mg·kg^(-1)·d^(-1) in XAN-H group)was administered to gavage for 14 d.Orbital blood was collected on the 3rd,7th,10th and 14th d to detect the levels of serum UA,creatinine(CRE),blood urea nitrogen(BUN),and activity of xanthinoxidase(XOD)in each group.At the end of the experiment,the activity of alkaline phosphatase(ALP),the levels of bone metabolism-related proteins such as Runt-related transcription factor 2(Runx 2),cathepsin K(CTSK),receptor activator of nuclear factor kappa B ligand(RANKL)and osteoprotegerin(OPG)were measured,and then the ratio of RANKL/OPG was analyzed.Results Compared with the blank group,the serum levels of UA in rats of model group were significantly increased on the 3rd,7th,10th and 14th d(all P<0.01),indicating that the HUA model was successfully constructed.Compared with the model group,both XAN-M and XAN-H effectively reduced the levels of serum UA in acute and chronic HUA rats(all P<0.01),inhibited the XOD activity(all P<0.01),and improved the renal function indexes CRE(all P<0.01)and BUN(all P<0.05).Although XAN-L did not significantly reduce the serum UA level in acute HUA rats,it effectively decreased the XOD activity(P<0.01)and improved its renal function indexes CRE(P<0.01)and BUN(P<0.05);while for chronic HUA rats,it had descending effects on the serum UA level(all P<0.01),but had no obvious renal

关 键 词：啤酒花 黄腐酚 高尿酸血症 尿酸 骨代谢 

分 类 号：R285.5[医药卫生—中药学]