基于高尿酸血症Wistar大鼠肾纤维化模型探讨ZAG与ERK1/2和p38MAPK信号通路的交互作用

打开文本图片集

中图分类号：R361 文献标志码：A DOI：10.3969/j.issn.1007-7146.2025.04.008

Exploring the Interaction of ZAG with ERK1/2 and p38 MAPK Signaling Pathways Based on the Hyperuricemic Wistar Rat Model ofRenal Fibrosis

FAN Kaixuan，ZHAN Yiting， YANGJie，CHENBingyuan，WAN Guangyang，ANMiaomiao，CHENBingpu （SchoolofBasic Medical Sciences，Youjiang Medical UniversityforNationalities，Baise 533ooo，China）

Abstract：To explore the mechanismby which zinc-α2-glycoprotein （ZAG）forms a feedback lop with extracelularsignalregulatedkinase1/2（ERK1/2）andp38mitogen-activated proteinkinase（p38MAPK）toregulaterenalepithelial-mesenchymal transition（EMT）inrenaltissueofhyperuricemia-inducedrenalfibrosisrats，64SPF-grademaleWistarrats weredividedinto anormalgroupandahyperuricemia group.HalfoftheratsineachgroupweresubjectedtoZAGoverexpressiontreatment to observethe interactionbetween ZAG expression levelsandERK1/2 andp38MAPK signalingpathways inrenal tisse.The results showedthatcompared withthenormalgroup，themRNAand proteinlevelsofEMT-related molecules intherenaltissue of the hyperuricemia group were significantly upregulated.In the hyperuricemia group，ZAGoverexpresionreduced theserum uric acid （SUA）level，alevatedaldyfunction，ndelaedteprogresioofnalfosisineuriceicopathy rats.Meanwhile，ZAGoverexpressionsignificantlydecreasedtheexpresionofrelatedproteinsandtheirmRNAintemitogenactivated protein kinase （MAPK）pathwayintherenal isueofhyperuricemic nephropathyrats.Thefindings indicatethat ZAG overexpression inhibits theactivationofERK1/2andp38MAPK signaling pathwaysand delaysthe processofEMT，thereby aleviatingrenalinjuryandfibrosiscausedbyhyperuricemiaandeducinghyperuricemicnephropathyinrats.Theseresultsopen up a new research prospect for the potential preventive effect of ZAG on hyperuricemic nephropathy.

Key Words： ZAG; p38 MAPK; ERK1/2; renal fibrosis; epithelial-mesenchymal transition; hyperuricemic nephropathy （ActaLaser BiologySinica，2025，34（4）：354-364）

尿酸是嘌呤代谢的终产物，在肝脏中生成，并通过肾脏和肠道排泄。（剩余17084字）