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雷公藤多苷调控 HIF-1α/miR-155-5p/Nrf2 通路改善大鼠肾病综
合征的机制研究
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陶伊璠 1, 2* ,宋纯东 1, 2 # ,王 旭 ,张 冲 ,苏 颖 ,郏溪栋 ,姜浩然 (1.河南中医药大学第一附属医院
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儿科医院肾病紫癜二病区,郑州 450000;2.河南中医药大学儿科医学院,郑州 450046)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2026)05-0602-05
DOI 10.6039/j.issn.1001-0408.2026.05.09
摘 要 目的 研究雷公藤多苷(TWM)对大鼠肾病综合征的改善作用机制。方法 采用尾静脉注射阿霉素的方法复制肾病综合
征模型大鼠。将造模成功的大鼠随机分为模型组(蒸馏水)、泼尼松组(10 mg/kg)和TWM高、低剂量组(10、5 mg/kg),另设置不造
模的空白组(蒸馏水),每组9只。各组大鼠灌胃相应药液/蒸馏水,每天1次,连续6周。观察大鼠肾组织病理学形态;检测大鼠24
h尿蛋白(24 h-UTP)和血清中生化指标[白蛋白(ALB)、血尿素氮(BUN)、肌酐(SCr)、总胆固醇(CHOL)、甘油三酯(TG)]水平;检
测大鼠肾组织中氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)]水平;检测大鼠肾组织中缺氧诱导因子1α(HIF-1α)/微小
RNA-155-5p(miR-155-5p)/核因子E2相关因子2(Nrf2)信号通路相关mRNA和蛋白表达水平。结果 与空白组比较,模型组大鼠肾
组织结构紊乱,肾小球少量坏死,肾小管上皮细胞水肿;24 h-UTP,血清中SCr、BUN、CHOL、TG水平,肾组织中MDA水平,肾组织
中HIF-1α、Kelch样ECH相关蛋白1(Keap1)mRNA和蛋白表达水平以及miR-155-5p表达水平均显著升高(P<0.05);血清中ALB
水平、肾组织中SOD水平以及Nrf2 mRNA和蛋白表达水平均显著降低(P<0.05)。与模型组比较,TWM高、低剂量组大鼠肾损伤
明显改善,上述定量指标水平均显著逆转(P<0.05)。结论 TWM可通过调控HIF-1α/miR-155-5p/Nrf2信号通路,减轻氧化应激损
伤,从而改善大鼠肾病综合征。
关键词 雷公藤多苷;肾病综合征;氧化应激;HIF-1α/miR-155-5p/Nrf2信号通路
Mechanistic study of Tripterygium wilfordii multiglucoside in improving nephrotic syndrome via regulating
the HIF-1α/miR-155-5p/Nrf2 pathway
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TAO Yifan ,SONG Chundong ,WANG Xu ,ZHANG Chong ,SU Ying ,JIA Xidong ,JIANG Haoran 1, 2
(1. Second Ward of Nephropathy Purpura, Pediatric Hospital, the First Affiliated Hospital of Henan University
of Chinese Medicine, Zhengzhou 450000, China;2. School of Pediatrics, Henan University of Chinese
Medicine, Zhengzhou 450046, China)
ABSTRACT OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside (TWM) on
nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via
the tail vein. The modeling rats were randomly divided into the model group (distilled water), prednisone group (10 mg/kg), and
TWM high- and low-dose groups (10 and 5 mg/kg, respectively). Additionally, blank group (distilled water) without model
induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled
water by gavage, once a day, for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed;
the levels of 24-hour urinary protein (24 h-UTP) and serum biochemical indicators [albumin (ALB), blood urea nitrogen (BUN),
serum creatinine (SCr), cholesterol (CHOL), and triglyceride (TG)] in rats were determined; the levels of oxidative stress
indicators [superoxide dismutase (SOD), malondialdehyde (MDA)] in kidney tissue of rats were determined; expressions of
hypoxia-inducible factor-1α (HIF-1α)/microRNA-155-5p
Δ 基金项目 国家自然科学基金面上项目(No.82074493);河南省 (miR-155-5p)/nuclear factor erythriod 2- related factor 2
卫 生 健 康 委 员 会 河 南 省 中 医 药 科 学 研 究 专 项 重 点 课 题(No. (Nrf2) signaling pathway-related mRNA and protein in the
2024ZY1002);河南省卫生健康委员会国家中医药传承创新中心联合 renal tissues of rats were detected. RESULTS Compared with
共建科研专项立项(No.2024ZXZX1019);河南中医药大学“仲景三名
the blank group, the rats in the model group exhibited
人才工程”仲景领军名医项目(No.河中医政〔2025〕116号) disordered renal tissue structure, with a small amount of
*第一作者 硕士研究生。研究方向:儿童肾脏病及风湿免疫性疾
glomerular necrosis and edema of the renal tubular epithelial
病。E-mail:t17518874849@163.com
# 通信作者 教授,主任医师,博士生导师,博士。研究方向:儿童 cells. 24 h-UTP, serum levels of SCr, BUN, CHOL and TG,
肾脏病及风湿免疫性疾病。E-mail:scd670918@126.com MDA content, mRNA and protein expressions of HIF-1α and
· 602 · China Pharmacy 2026 Vol. 37 No. 5 中国药房 2026年第37卷第5期

