[1]任永昊,王一川.吴茱萸碱调节音猬因子/家族锌指蛋白1通路对免疫球蛋白Ａ肾病大鼠肾损伤的影响[J].陕西医学杂志,2025,54(10):1299-1304.[doi:DOI:10.3969/j.issn.1000-7377.2025.10.001]
　REN Yonghao,WANG Yichuan.Effect of evodiamine on renal damage in IgA nephropathy rats by modulating Shh/Gli1 pathway[J].,2025,54(10):1299-1304.[doi:DOI:10.3969/j.issn.1000-7377.2025.10.001]
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吴茱萸碱调节音猬因子/家族锌指蛋白1通路对免疫球蛋白Ａ肾病大鼠肾损伤的影响

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年10期
页码:
1299-1304
栏目:
基础研究
出版日期:
2025-10-05

文章信息/Info

Title:
Effect of evodiamine on renal damage in IgA nephropathy rats by modulating Shh/Gli1 pathway
作者:
任永昊; 王一川
（山东中医药大学附属医院肾内二科，山东 济南 250014）
Author(s):
REN Yonghao; WANG Yichuan
(Department of Nephrology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China)
关键词:
吴茱萸碱; 免疫球蛋白Ａ肾病; 音猬因子; Gli家族锌指蛋白1; 肾损伤; 作用机制
Keywords:
Evodiamine; Immunoglobulin A nephropathy; Sonic hedgehog; Glioma-associated oncogene homolog 1; Renal damage; Mechanism of action
分类号:
R 692
DOI:
DOI:10.3969/j.issn.1000-7377.2025.10.001
文献标志码:
A
摘要:
目的：探讨吴茱萸碱（Evo）调节音猬因子（Shh）/Gli家族锌指蛋白1（Gli1）通路对免疫球蛋白Ａ肾病（IgAN）大鼠肾损伤的影响。方法：将SD大鼠随机分为NC组、IgAN组、L-Evo组（20 mg/kg Evo）、H-Evo组（40 mg/kg Evo）、H-Evo+PUR组（40 mg/kg Evo+5 mg/kg Shh激活剂Purmorphamine）。全自动生化分析仪测定各组尿液中24 h尿蛋白、尿红细胞及血清中血肌酐、血尿素氮、白蛋白水平。ELISA测定各组血清中肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）水平，HE染色观察各组肾组织的病理学形态，免疫荧光染色观察各组肾组织中IgA、α-平滑肌肌动蛋白（α-SMA）表达水平，Western blot检测各组肾组织中Shh、Gli1及细胞外基质沉积相关蛋白表达。结果：与NC组比较，IgAN组尿液中24 h尿蛋白、尿红细胞及血清中血肌酐、血尿素氮、TNF-α、IL-1β水平上升，肾组织病理损伤严重，且肾组织中IgA、α-SMA、Shh、Gli1、纤连蛋白（Fibronectin）、胶原蛋白（Collagen）、层粘连蛋白（Laminin）水平上升，而血清中白蛋白水平下降（均P<0.05）；与IgAN组比较，L-Evo组、H-Evo组尿液中24 h尿蛋白、尿红细胞及血清中血肌酐、血尿素氮、TNF-α、IL-1β水平下降，肾组织病理损伤减轻，且肾组织中IgA、α-SMA、Shh、Gli1、Fibronectin、Collagen、Laminin水平下降，而血清中白蛋白水平上升（均P<0.05）；与H-Evo组比较，H-Evo+PUR组尿液中24 h尿蛋白、尿红细胞及血清中血肌酐、血尿素氮、TNF-α、IL-1β水平上升，肾组织病理损伤严重，且肾组织中IgA、α-SMA、Shh、Gli1、Fibronectin、Collagen、Laminin水平上升，而血清中白蛋白水平下降（均P<0.05）。结论：Evo可能通过抑制Shh/Gli1通路，抑制炎症反应，减少IgA、α-SMA的表达及细胞外基质的沉积，阻碍肾纤维化过程，改善肾组织的病理损伤。
Abstract:
Objective:To explore the effect of evodiamine (Evo) on renal damage in immunoglobulin A nephropathy (IgAN) rats by modulating sonic hedgehog (Shh)/Glioma-associated oncogene homolog 1 (Gli1) pathway.Methods：SD rats were stochastically assigned into NC group,IgAN group,L-Evo group (20 mg/kg Evo),H-Evo group (40 mg/kg Evo),and H-Evo+PUR group (40 mg/kg Evo+5 mg/kg Shh activator Purmorphoamine).Fully automated biochemical analyzer was used to measure urine 24-hour urine protein,urine red blood cells,and serum creatinine,blood urea nitrogen,and albumin in each group.ELISA was used to measure serum tumor necrosis factor α (TNF-α) and interleukin 1β(IL-1β) in each group,and HE staining was used to observe the pathological morphology of renal tissue in each group.Immunofluorescence staining was used to observe IgA and α-SMA in renal tissues of each group.Western blot was used to detect Shh,Gli1,and extracellular matrix deposition related proteins in kidney tissues of each group.Results:For the NC group,the IgAN group showed an increase in 24-hour urine protein,urine red blood cells,and serum creatinine,blood urea nitrogen,TNF-α,and IL-1β,severe renal tissue pathological damage,an increase in IgA,α-SMA,Shh,Gli1,Fibronectin,Collagen,and Laminin in renal tissue,and a decrease in serum albumin (all P<0.05).For the IgAN group,the L-Evo group and H-Evo group showed a decrease in 24-hour urine protein,urine red blood cells,and serum creatinine,blood urea nitrogen,TNF-α,and IL-1β,reduced renal tissue pathological damage,a reduction in IgA,α-SMA,Shh,Gli1,Fibronectin,Collagen,and Laminin in renal tissue,and a raise in serum albumin (all P<0.05).For the H-Evo group,the H-Evo+PUR group showed an increase in 24-hour urine protein,urine red blood cells,and serum creatinine,blood urea nitrogen,TNF-α,and IL-1β,severe renal tissue pathological damage,an increase in IgA,α-SMA,Shh,Gli1,Fibronectin,Collagen,and Laminin in renal tissue,and a decrease in serum albumin (all P<0.05).Conclusion:Evo may inhibit Shh/Gli1 pathway,suppress inflammatory responses,reduce IgA,α-SMA,and extracellular matrix deposition,hinder the process of renal fibrosis,and improve pathological damage to renal tissue.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（82204881）
更新日期/Last Update: 2025-10-09