中国临床药理学杂志

益肾祛风方通过调节Nrf2/HO-1介导的铁死亡改善单侧输尿管梗阻大鼠肾纤维化的研究

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高晶琳 ¹^,²^,³^,⁴ , 韦缘 ¹^,²^,³^,⁴ , 周恩超 ¹^,²^,³^,⁴

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(17): 2489-2495

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (17) : 2489 -2495

益肾祛风方通过调节Nrf2/HO-1介导的铁死亡改善单侧输尿管梗阻大鼠肾纤维化的研究

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高晶琳¹^,²^,³^,⁴, 韦缘¹^,²^,³^,⁴, 周恩超¹^,²^,³^,⁴

作者信息

^1.南京中医药大学附属医院/江苏省中医院肾内科，江苏南京 210029

^2.南京中医药大学第一临床医学院，江苏南京 210046

^3.中医补益肾元抗衰老研究江苏高校重点实验室，江苏南京 210023

^4.国医大师邹燕勤传承工作室，江苏南京 210029

通讯作者:

周恩超，主任中医师 Tel: （025）86617141 E-mail: zhouenchao@njucm.edu.cn

作者简介:

高晶琳（1999-），女，硕士研究生，主要从事中医肾病的临床诊断及相关基础研究

Research of Yishen Qufeng formulation ameliorates renal fibrosis in unilateral ureteral obstruction rats by regulating Nrf2/HO-1-mediated ferroptosis

Jing-lin GAO¹^,²^,³^,⁴, Yuan WEI¹^,²^,³^,⁴, En-chao ZHOU¹^,²^,³^,⁴

Affiliations

^1.Department of Nephrology, Nanjing University of Traditional Chinese Medicine Affiliated Hospital / Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China

^2.First Clinical School, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, Jiangsu Province, China

^3.Key Laboratory of Traditional Chinese Medicine Tonifying Kidney Elements and Anti Aging Research in Jiangsu Universities, Nanjing 210023, Jiangsu Province, China

^4.Master of Traditional Chinese Medicine Zou Yanqin Inheritance Studio, Nanjing 210029, Jiangsu Province, China

出版时间: 2025-09-17 doi: 10.13699/j.cnki.1001-6821.2025.17.016

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摘要

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目的

通过构建单侧输尿管梗阻（UUO）大鼠肾纤维化模型，探究益肾祛风方（YQF）通过调节核因子红系2相关因子2（Nrf2）/血红素氧合酶-1（HO-1）轴介导铁死亡改善肾纤维化的机制。

方法

将8周龄SD大鼠随机分为假手术组、模型组、阳性对照组（20 mg·kg^-1·d^-1达格列净）和低、中、高剂量实验组（15.21、22.82和30.42 g·kg^-1·d^-1益肾祛风方）。除假手术组外，其余各组大鼠单侧结扎左侧输尿管构建肾间质纤维化（RIF）模型。待造模成功后，阳性对照组和低、中、高剂量实验组分别灌胃给予对应药物，假手术组和模型组均灌胃给予等体积的0.9%NaCl。6组大鼠每天给药1次，连续14 d。用全自动整合式生化分析仪检测血清肌酸酐、尿素氮和尿蛋白水平，用蛋白质印迹法检测肾组织中纤维化、氧化应激及铁死亡相关蛋白相对表达水平的变化。

结果

中、高剂量实验组、假手术组、模型组及阳性对照组的血清肌酸酐水平分别为（50.24±7.81）、（49.15±8.87）、（41.96±5.25）、（59.44±11.93）和（52.14±8.38）μmol·L^-1，尿素氮水平分别为（4.58±0.56）、（4.45±0.55）、（4.32±0.60）、（6.00±1.03）和（6.55±1.02）mmol·L^-1，尿蛋白水平分别为（640.59±205.70）、（538.74±237.98）、（526.51±192.62）、（982.91±349.13）和（964.26±456.84）mg·d^-1，谷胱甘肽过氧化物酶4（GPX4）蛋白相对表达水平分别为1.62±0.15、3.01±0.41、2.25±0.27、1.01±0.51和2.15±0.63，胱氨酸/谷氨酸反向转运体（xCT）蛋白相对表达水平分别为0.62±0.10、1.02±0.06、1.65±0.13、0.52±0.20和1.18±0.13，Nrf2蛋白相对表达水平分别为0.66±0.12、1.04±0.16、1.20±0.10、0.54±0.03和1.19±0.14，HO-1蛋白相对表达水平分别为1.13±0.15、1.21±0.18、2.21±0.17、0.64±0.44和1.57±0.26，α-平滑肌肌动蛋白（α-SMA）相对表达水平分别为1.63±0.47、1.13±0.57、0.49±0.91、2.88±0.97和1.05±0.60，高剂量实验组的上述指标与模型组比较，在统计学上差异均有统计学意义（均P<0.05）。

结论

益肾祛风方可能通过激活Nrf2/HO-1信号通路抑制铁死亡进而有效缓解UUO大鼠的肾间质纤维化。

关键词

益肾祛风方 / 肾纤维化 / 慢性肾病 / 铁死亡 / 单侧输尿管梗阻大鼠

Abstract

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Objective

To establish a rat model of renal fibrosis induced by unilateral ureteral obstruction (UUO), and investigate the mechanism of the Yishen Qufeng Formula (YQF) improves renal fibrosis through regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis to mediate ferroptosis.

Methods

Eight-week-old SD rats were randomly divided into the sham-operation group, model group, positive control group (dapagliflozin at 20 mg·kg^-1·d^-1), and experimental -L,-M,-H groups (Yishen Qufeng Formula at 15.21, 22.82 and 30.42 g·kg^-1·d^-1). Except for the sham operation group, rats in the other groups were subjected to left ureteral ligation to establish a renal interstitial fibrosis (RIF) model. After successful modeling, the positive control group and the -L, -M, and -H dose experimental groups were given the corresponding drugs by gavage, while the sham operation group and model group were given an equal volume of 0.9% NaCl by gavage. All rats in the 6 groups were administered once a day for 14 consecutive days. Serum creatinine, urea nitrogen and urine protein levels were detected using a fully automatic integrated biochemical analyzer. The content of transforming growth factor-β1 (TGF-β1) was measured by enzyme-linked immunosorbent assay (ELISA). The changes in the relative expression levels of fibrosis-related, oxidative stress-related and ferroptosis-related proteins in renal tissues were determined by Western blotting.

Results

The levels of serum creatinine in the experimental -M, -H groups, sham operation group, model group and positive control group were (50.24±7.81), (49.15±8.87), (41.96±5.25), (59.44±11.93) and (52.14±8.38)μmol·L^-1, respectively; the levels of urea nitrogen were (4.58±0.56), (4.45±0.55), (4.32±0.60), (6.00±1.03) and (6.55±1.02)mmol·L^-1, respectively; the levels of urine protein were (640.59±205.70), (538.74±237.98), (526.51±192.62), (982.91±349.13) and (964.26±456.84)mg·d^-1, respectively; the relative protein expression levels of glutathione peroxidase 4 (GPX4) were 1.62±0.15, 3.01±0.41, 2.25±0.27, 1.01±0.51 and 2.15±0.63, respectively; the relative protein expression levels of cystine/glutamate antiporter (xCT) were 0.62±0.10, 1.02±0.06, 1.65±0.13, 0.52±0.20 and 1.18±0.13, respectively; the relative protein expression levels of Nrf2 were 0.66±0.12, 1.04±0.16, 1.20±0.10, 0.54±0.03 and 1.19±0.14, respectively; the relative protein expression levels of HO-1 were 1.13±0.15, 1.21±0.18, 2.21±0.17, 0.64±0.44 and 1.57±0.26, respectively; the relative protein expression levels of α-smooth muscle actin (α-SMA) were 1.63±0.47, 1.13±0.57, 0.49±0.91, 2.88±0.97 and 1.05±0.60, respectively. There were statistically significant differences in the above indicators between the high-dose experimental group and the model group (all P<0.05).

Conclusion

Yishen Qufeng Formula may inhibit ferroptosis by activating the Nrf2/HO-1 signaling pathway, thereby effectively alleviating renal interstitial fibrosis in UUO rats. This provides important theoretical evidence for the mechanism by which the Yishen Qufeng Formula improves renal fibrosis through regulation of ferroptosis.

Key words

Yishen Qufeng Formula / renal fibrosis / chronic kidney disease / ferroptosis / unilateral ureteral obstruction rats

引用本文

高晶琳, 韦缘, 周恩超. 益肾祛风方通过调节Nrf2/HO-1介导的铁死亡改善单侧输尿管梗阻大鼠肾纤维化的研究. 中国临床药理学杂志, 2025 , 41 (17) : 2489 -2495 . DOI: 10.13699/j.cnki.1001-6821.2025.17.016

Jing-lin GAO, Yuan WEI, En-chao ZHOU. Research of Yishen Qufeng formulation ameliorates renal fibrosis in unilateral ureteral obstruction rats by regulating Nrf2/HO-1-mediated ferroptosis[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (17) : 2489 -2495 . DOI: 10.13699/j.cnki.1001-6821.2025.17.016

基金

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国家自然科学基金面上基金资助项目(82474427)
第三批江苏省中医药领军人才基金资助项目(SLJ0319)
江苏省研究生实践创新计划基金资助项目(KYCX24-2232)
江苏省中医院科技基金资助项目(Y2022zj07)
江苏省中医院院级课题面上基金资助项目(Y2202)

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2025年第41卷第17期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.17.016

接收时间：2025-04-05
首发时间：2026-08-05
出版时间：2025-09-17

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收稿日期：2025-04-05

基金

国家自然科学基金面上基金资助项目(82474427)

第三批江苏省中医药领军人才基金资助项目(SLJ0319)

江苏省研究生实践创新计划基金资助项目(KYCX24-2232)

江苏省中医院科技基金资助项目(Y2022zj07)

江苏省中医院院级课题面上基金资助项目(Y2202)

作者信息

^1.南京中医药大学附属医院/江苏省中医院肾内科，江苏南京 210029

^2.南京中医药大学第一临床医学院，江苏南京 210046

^3.中医补益肾元抗衰老研究江苏高校重点实验室，江苏南京 210023

^4.国医大师邹燕勤传承工作室，江苏南京 210029

通讯作者:

周恩超，主任中医师 Tel: （025）86617141 E-mail: zhouenchao@njucm.edu.cn

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.17.016

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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