安徽中医药大学学报2024,Vol.43Issue(6) :68-73.DOI:10.3969/j.issn.2095-7246.2024.06.015

降浊颗粒介导缺氧诱导因子-1α途径改善单侧输尿管阻塞模型肾纤维化

Jiangzhuo Granule Improves Renal Fibrosis in a Model of Unilateral Ureteral Obstruction by Mediating the Hypoxia-inducible Factor-1α Pathway

杨蕾 孟凤仙 王达利 王洁 张红红 张正菊 陆清怡
安徽中医药大学学报2024,Vol.43Issue(6) :68-73.DOI:10.3969/j.issn.2095-7246.2024.06.015

降浊颗粒介导缺氧诱导因子-1α途径改善单侧输尿管阻塞模型肾纤维化

Jiangzhuo Granule Improves Renal Fibrosis in a Model of Unilateral Ureteral Obstruction by Mediating the Hypoxia-inducible Factor-1α Pathway

杨蕾 1孟凤仙 2王达利 3王洁 4张红红 4张正菊 2陆清怡5
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作者信息

  • 1. 北京中医药大学第三附属医院,北京 100029
  • 2. 北京中医药大学东方医院,北京 100078
  • 3. 北京市房山区燕山地区社区卫生服务中心,北京 102500
  • 4. 北京中医医院顺义医院,北京 101300
  • 5. 北京中医药大学生命科学学院,北京 102400
  • 折叠

摘要

目的 从缺氧诱导因子(hypoxia inducible factors,HIF)-1α途径探究降浊颗粒改善肾纤维化的作用机制.方法 采用单侧输尿管梗阻(unilateral ureteral obstruction,UUO)法复制肾纤维化模型.将肾纤维化大鼠随机分为模型组、阳性药组、降浊颗粒组,每组6只,另将6只同规格大鼠作为假手术组.连续干预4周后,采用苏木精—伊红染色、Masson染色观察肾组织形态学变化,测定4组大鼠尿肌酐(creatinine,Cr)、尿蛋白(urinary protein,uPr)、尿微量白蛋白(microalbuminuria,MAU)水平,血液中尿酸(uric acid,UA)、Cr和血尿素氮(blood urea nitro-gen,BUN)水平,采用ELISA法检测血清白细胞介素(interleukin,IL)-1β、IL-18、肿瘤坏死因子(tumor necrosis fac-tor,TNF)-α、单核细胞趋化蛋白(monocyte chemotactic protein,MCP)-1、α1微球蛋白(α1-microglobulin,α1-MG)、视黄醇结合蛋白(retinol-binding protein,RBP)-4表达水平,采用Western blot法检测肾组织中HIF-1α、TGF-β1蛋白表达水平.结果 降浊颗粒可明显抑制UUO大鼠肾间质胶原纤维增生,显著降低UUO大鼠尿Cr、uPr、MAU水平,血液中Cr、UA、α1-MG、IL-1β、IL-18、MCP-1、TNF-α和BUN水平,以及肾组织中HIF-1α、TGF-β1水平(P<0.05).结论 降浊颗粒抑制UUO大鼠肾间质纤维化进程、保护肾功能的作用机制,可能与抑制免疫炎症反应、调控HIF-1α途径有关.

Abstract

Objective To investigate the mechanism of action of Jiangzhuo Granule in improving renal fibrosis via the hypoxia-inducible factor 1α(HIF-1α)pathway.Methods The unilateral ureteral obstruction (UUO)method was used to establish a model of renal fibrosis.The rats with renal fibrosis were randomly divided into model group,positive drug group,and Jiang-zhuo Granule group,with 6 rats in each group,and another 6 rats of the same size were selected as the sham-operation group.After 4 weeks of continuous intervention,HE staining and Masson staining were used to observe renal histomorphological changes,and the levels of creatinine (Cr),urinary protein (uPr),and microalbuminuria (MAU)were measured,as well as the levels of uric acid (UA),blood urea nitrogen (BUN),and Cr in blood;ELISA was used to measure the protein expression levels of interleukin-1β(IL-1β),interleukin-18 (IL-18 ),tumor necrosis factor-α(TNF-α),monocyte chemotactic protein-1 (MCP-1 ),α1-microglobulin (α1-MG),and retinol-binding protein-4 (RBP-4)in serum,and Western blot was used to measure the protein expression levels of HIF-1α and transforming growth factor-beta 1 (TGF-β1)in renal tissue.Results Jiangzhuo Granule sig-nificantly inhibited the proliferation of collagen fibers in the renal interstitium of UUO rats and significantly reduced the levels of urinary Cr,uPr,and MAU,the levels of Cr,BUN,UA,α1-MG,IL-1β,IL-18,MCP-1,and TNF-α in blood,and the levels of HIF-1α and TGF-β1 in renal tissue (P<0.05).Conclusion Jiangzhuo Granule can inhibit the progression of renal interstitial fibrosis and pro-tects renal function in UUO rats,possibly by inhibiting immune inflammatory response and regulating the HIF-1α pathway.

关键词

降浊颗粒/肾纤维化/缺氧诱导因子-1α/炎症因子

Key words

Jiangzhuo Granule/Renal fibrosis/Hypoxia-inducible factor-1α/Inflammatory factor

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出版年

2024
安徽中医药大学学报
安徽中医学院

安徽中医药大学学报

CSTPCD
影响因子:0.796
ISSN:2095-7246
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