南京中医药大学学报2025，Vol.41Issue(7)：914-925,12.DOI:10.14148/j.issn.1672-0482.2025.0914
祛浊通痹颗粒对高尿酸血症小鼠降尿酸作用的研究
Research on the Hypouricemic Effect of Quzhuo Tongbi Granules on Mice with Hyperuricemia
摘要
Abstract
OBJECTIVE To investigate the mechanism of action of Quzhuo Tongbi Granules(QZTB)in reducing uric acid and anti-inflammation in mice with hyperuricemia(HUA).METHODS The components of QZTB were identified by ultra-performance liquid chromatography-mass spectrometry(UPLC-MS).Sixty-four C57BL/6 mice were randomly divided into control group,model group,benzbromarone group,QZTB low-dose group,QZTB medium-dose group,QZTB high-dose group,MCC950 group,and MCC950+QZTB medium-dose group,with 8 mice in each group.Adenine(100 mg·kg-1)and potassium oxonate(500 mg·kg-1)were used to establish the HUA mouse model.Except for the control group,all other groups underwent 2 weeks of modeling followed by 4 weeks of treatment.After 2 weeks of modeling,blood was collected from the orbital venous plexus to measure serum uric acid(SUA)levels as the criterion for successful model induction.Mice were sacrificed after 4 weeks of continuous treatment for sample collection.An automatic biochemical analyzer was used to measure serum levels of SUA,urea nitrogen(BUN),and creatinine(Cr).Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-18(IL-18),and tumor necrosis factor-α(TNF-α).The qPCR was used to assess mRNA expression of urate transporter 1(URAT1),ATP-binding cassette transporter G2(ABCG2),glucose transporter 9(GLUT9),and PDZ domain-contai-ning protein kinase 1(PDZK1)in kidney tissue.Western blot was performed to measure protein expression of urate transporters(URAT1,ABCG2,GLUT9,PDZK1),nuclear transcription factor κB(NF-κB)total protein,phosphorylated NF-κB(p-NF-κB),Nod-like receptor protein 3(NLRP3),Cleaved Caspase-1 and Pro-Caspase-1 proteins in kidney tissue.Immunohistochemistry was used to determine the expression levels of urate transporters(URAT1,ABCG2,PDZK1,GLUT9)in kidney tissue.RESULTS A to-tal of 9 representative active ingredients were identified in QZTB.Two weeks after modeling,SUA in the model group was significantly increased compared with that in the control group(P<0.000 1).Four weeks after administration,serum SUA,BUN and Cr in the model group were significantly increased(P<0.000 1),IL-1β,IL-6,IL-18 and TNF-α levels were increased(P<0.01,P<0.001),the expression of ABCG2 and PDZK1 proteins in renal tissue was decreased(P<0.01,P<0.001,P<0.000 1),and the ex-pression of URAT1,GLUT9,NLRP3,p-NF-κB p65/NF-κB p65 and Cleaved Caspase-1/Pro-Caspase-1 proteins was significantly increased(P<0.01,P<0.001,P<0.000 1).Compared with the model group,SUA,BUN and Cr in the benzbromarone group and the low-,medium-and high-dose QZTB intervention groups were reduced to varying degrees(P<0.001,P<0.000 1).QZTB could ef-fectively reduce the levels of serum inflammatory factors IL-1β,IL-6,IL-18 and TNF-α(P<0.05,P<0.01),increase the expres-sion of ABCG2 and PDZK1 proteins in renal tissue(P<0.05,P<0.01,P<0.000 1),and downregulate the expression of URAT1,GLUT9,NLRP3,p-NF-κB p65/NF-κB p65 and Cleaved Caspase-1/Pro-Caspase-1 proteins(P<0.05,P<0.01,P<0.001,P<0.000 1).Compared with the model group,the MCC950 group downregulated the protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and Cleaved Caspase-1/Pro-Caspase-1(P<0.01).Compared with the MCC950 group or the QZTB group,the MCC950+QZTB group downregulated the protein expressions of NLRP3,p-NF-κB p65/NF-κB p65,and Cleaved Caspase-1/Pro-Caspase-1(P<0.05,P<0.01,P<0.000 1).CONCLUSION QZTB can promote uric acid excretion by inhibiting the NF-κB/NLRP3 signaling pathway,thereby improving the symptoms of HUA.关键词
祛浊通痹颗粒/高尿酸血症/尿酸转运体/NF-κB/NLRP3炎症小体/Caspase-1Key words
Quzhuo Tongbi Granules/hyperuricemia/uric acid transporter/NF-κB/NLRP3 inflammasome/Caspase-1分类
医药卫生引用本文复制引用
阮熙,周俊祺,李海昌,宋黎喆雄,胡轩铭..祛浊通痹颗粒对高尿酸血症小鼠降尿酸作用的研究[J].南京中医药大学学报,2025,41(7):914-925,12.基金项目
中国博士后科学基金第73批面上资助项目(2023M733192) （2023M733192）
"十四五"国家重点研发计划"中医药现代化"重点专项(2022YFC3501200) （2022YFC3501200）
浙江中医药大学2023年校级科研项目(2023JKZKTS09) （2023JKZKTS09）
