中国临床药理学杂志2025，Vol.41Issue(17)：2483-2488,6.DOI:10.13699/j.cnki.1001-6821.2025.17.015
高尿酸血症加剧对乙酰氨基酚所致肝损伤的作用和机制研究
Research on the aggravating effect and mechanism of hyperuricemia on acetaminophen-induced liver injury
摘要
Abstract
Objective To explore the effect and potential mechanism of hyperuricemia(HUA)on acetaminophen(APAP)-induced liver injury.Methods Male mice were randomly divided into four groups:group A(control),group B[establishment of a hyperuricemia(HUA)model],group C(administered by oral gavage at a dose of 300 mg·kg-1 APAP),and group D(establishment of a HUA model combined with administered by oral gavage at a dose of 300 mg·kg-1 APAP).The HUA model was established by intraperitoneal injection of potassium oxonate(350 mg·kg-1)and gavage of xanthine(450 mg·kg-1)for 14 consecutive days.On day 13,mice in group C and group D received APAP via gavage.All mice were sacrificed 24 h later.Serum levels of uric acid(UA),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were determined by biochemical analyzer.Liver histopathology was evaluated by hematoxylin-eosin(H&E)staining.Levels of malondialdehyde(MDA),reactive oxygen species(ROS),glutathione(GSH),interleukin-1(3(IL-1 β)and tumor necrosis factor-α(TNF-α)in liver tissues were measured using commercial kits.Immunofluorescence was used to detect the relative expression of nuclear factor erythroid 2-related factor 2(Nrf2).Results The serum uric acid levels in the group A,group B,group C and group D were(186.20±15.61),(521.50±56.81),(325.20±31.74)and(682.00±49.51)μmol·L-1,respectively;the liver coefficients were(4.51±0.14)％,(4.77±0.23)％,(4.98±0.21)％,and(5.51±0.30)％,respectively;the serum ALT levels were(55.80±15.86),(78.09±10.92),(27 688.81±7 166.01),and(34 571.89±7 793.74)U·L-1,respectively;the AST levels were(159.90±29.72),(143.70±26.46),(10 880.00±4 291.01),and(19 824.84±7 874.64)U·L-1,respectively;the hepatic MDA contents were(5.42±0.38),(7.77±0.32),(6.07±0.31),and(9.08±0.36)mol·g-1·prot-1,respectively;the ROS contents were(28.09±3.52),(39.67±2.70),(32.22±4.71),and(45.67±2.71)μg·g-1·prot-1,respectively;the GSH levels were(2.47±0.27),(1.72±0.16),(2.24±0.16),and(1.37±0.11)μg·g-1·prot-1,respectively;the IL-1β contents were(22.16±0.88),(31.74±1.82),(25.35±1.07),and(38.82±1.68)μg·g-1·prot-1,respectively;the TNF-α contents were(114.90±10.60),(180.20±3.72),(142.20±4.69),and(228.10±17.33)μg·g-1·prot-1,respectively;the relative protein expression of Nrf2 were 218.30±5.16,63.60±29.02,100.80±23.60,and 9.31±8.83,respectively.The indices in groups B and C were significantly different from those in group A,and the indices in group D were significantly different from those in group C,with all differences showing statistical significance(P＜0.05).Conclusion In the hyperuricemia(HUA)mouse model,the liver damage induced by acetaminophen(APAP)is aggravated,and this effect may be related to the downregulation of NRF2 expression.关键词
对乙酰氨基酚/高尿酸血症/肝损伤/核因子E2相关因子2Key words
acetaminophen/hyperuricemia/liver injury/nuclear factor erythroid 2-related factor 2分类
医药卫生引用本文复制引用
黄浩林,黎梦婷,周佑熙,张帅帅,庞建新,吴婷..高尿酸血症加剧对乙酰氨基酚所致肝损伤的作用和机制研究[J].中国临床药理学杂志,2025,41(17):2483-2488,6.基金项目
国家自然科学基金资助项目(82003819) （82003819）
广东省医学科研基金资助项目(A2023120) （A2023120）
