急性马兜铃酸中毒小鼠肾损伤及Wnt7b/β-catenin/MMP-7的表达变化  

Renal injury and expression of Wnt7b/β-catenin/MMP-7 in mice with acute aristolochic acidosis

作　　者：王一凡 刘爽 汪思齐 李茂娟 黄春华 楼迪栋 WANG Yifan;LIU Shuang;WANG Siqi;LI Maojuan;HUANG Chunhua;LOU Didong(Department of Forensic Medicine,Guizhou University of Chinese Medicine/Guizhou University of Traditional Chinese Medicine Forensic Institute,Guiyang 550000,China;Guizhou Provincial Key Laboratory of Forensic Medicine Toxicology,Guiyang 550000,China)

机构地区：[1]贵州中医药大学基础医学院法医学教研室/贵州中医药大学司法鉴定所,贵阳550000 [2]贵州省法医中药毒理学特色重点实验室,贵阳550000

出　　处：《中国医科大学学报》2023年第6期505-511,共7页Journal of China Medical University

基　　金：贵州省教育厅自然科学研究(黔教合KY字[2021]004);贵州省基础研究计划(黔科合基础-ZK[2022]一般465)。

摘　　要：目的连续观察急性马兜铃酸Ⅰ(AAⅠ)中毒小鼠肾损伤的病理改变和Wnt通路相关蛋白的表达,探讨Wnt7b信号通路参与马兜铃酸肾病(AAN)损伤修复的机制。方法观察小鼠暴露于AAⅠ后不同时间肾功能的变化,HE和Masson染色观察肾脏病理改变及纤维化情况,免疫组化和电镜观察Wnt7b信号通路相关蛋白的组织和亚细胞的定位和表达。结果小鼠暴露于AAⅠ后血肌酐和尿素氮增多;肾近端小管上皮细胞(PCTEC)刷状缘绒毛脱落、细胞水肿、坏死,小管基底膜裸露、纤维化加重;免疫组化和电镜结果显示,小鼠暴露于AAⅠ后,Wnt7b蛋白在PCTEC的刷状缘聚集,β-catenin的表达从细胞膜下转移至胞质和细胞核内,基质金属蛋白酶-7(MMP-7)表达增多,改变呈时间依赖性(P<0.05)。结论小鼠暴露于AAⅠ后肾脏生理功能异常,PCTEC坏死脱落,在此过程中Wnt7b信号通路被启动,β-catenin和MMP-7蛋白表达量增高。Objective To explore the mechanism of Wnt7b signaling pathway in the repair of aristolochic acidⅠ(AAⅠ)-induced acute kidney injury by observing the pathological changes in the kidney and the expression of Wnt pathway-related proteins in mice.Methods Alterations in renal function in mice at different times after exposure to AAⅠwere monitored,the pathological and fibrosis conditions of the kidney were visualized through HE and Masson staining,and the tissue and subcellular localization,and expression of proteins associated with the Wnt7b signaling pathway were analyzed via immunohistochemistry and electron microscopy.Results Mice exposed to AAⅠshowed increased levels of serum creatinine and urea nitrogen,along with shedding of the brush border villi in renal proximal tubular epithelial cells(PCTEC),cellular edema,necrosis,exposure of the tubular basement membrane,and aggravated fibrosis.Immunohistochemical and electron microscopy results revealed accumulation of Wnt7b protein in the brush border of PCTEC after exposure to AAⅠ,a shift inβ-catenin expression from the subcellular membrane to the cytoplasm and nucleus,and a time-dependent increase in MMP-7 expression(P<0.05).Conclusion After exposure to AAⅠ,the renal physiological function of mice was impaired,and proximal tubular epithelial cells underwent necrosis and abscission.At this point,the Wnt7b signaling pathway was initiated,and the expression ofβ-catenin and MMP-7 proteins increased.

关 键 词：急性马兜铃酸肾病 近端小管 Wnt7b/β-catenin 基质金属蛋白酶-7 损伤与修复 

分 类 号：R364[医药卫生—病理学]