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-1αPathway

作　　者：杨蕾 孟凤仙[2] 王达利 王洁 张红红 张正菊 陆清怡 YANG Lei;MENG Fengxian;WANG Dali;WANG Jie;ZHANG Honghong;ZHANG Zhengju;LU Qingyi(The Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China;Yanshan Community Health Service Center of Fangshan District,Beijing 102500,China;Beijing Hospital of Traditional Chinese Medicine Shunyi Branch,Beijing 101300,China;School of Life Sciences,Beijing University of Chinese Medicine,Beijing 102400,China)

机构地区：[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

出　　处：《安徽中医药大学学报》2024年第6期68-73,共6页Journal of Anhui University of Chinese Medicine

基　　金：国家重点研发计划项目(2023YFC3503003);国家自然科学基金项目(81904190);北京中医药大学“揭榜挂帅”项目(2023-JYB-JBQN-019)。

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 nitrogen,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 factor,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。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 Jiangzhuo 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-1αand transforming growth factor-beta 1(TGF-β1)in renal tissue.Results Jiangzhuo Granule significantly 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-αin blood,and the levels of HIF-1αand TGF-β1 in renal tissue(P<0.05).Conclusion Jiangzhuo Granule can inhibit the progression of renal interstitial fibrosis and protects renal function in UUO rats,possibly by inhibiting immune inflammatory response and regulating the HIF-1αpathway.

关 键 词：降浊颗粒 肾纤维化 缺氧诱导因子-1Α 炎症因子 

分 类 号：R285.5[医药卫生—中药学]