Original Articles

No. 2 Kangxianling decoction (抗纤灵二号方) protects against renal ischemia/reperfusion injury by hypoxia-inducible factor activation

  • YU Kena ,
  • ZHONG Liping ,
  • LIN Xiaomeng ,
  • CHEN Jian ,
  • HE Liqun ,
  • CAI Xudong
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  • 1 Department of Nephrology, Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo 315000, China
    2 Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
    3 Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200013, China
    4 Department of Nephrology, Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Wuhan 430000, China
    5 Department of Traditional Medicine, Shanghai Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
Prof. CAI Xudong, Department of Nephrology, Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo 315000, China, xudongcai1979@hotmail.com;
Prof. HE Liqun, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China; Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200013, China, heliqun59@163.com. Telephone: +86-574-89085041

Received date: 2024-11-19

  Accepted date: 2025-06-10

  Online published: 2026-04-04

Supported by

National Natural Science Foundation of China: Research on The Pathogenesis of Renal Micro Syndrome Accumulation in Chronic Renal Failure through Mammalian Target of Rapamycin Signaling Pathway and the Anti-fibrotic Effect of Kangxianling Decoction on Gene Knockout Mice(81373615);Zhejiang Natural Science Foundation of China: Mechanism Study of Wenyangxiaozheng Decoction Alleviating Cellular Senescence and Ameliorating Renal Fibrosis by Regulating the Phosphatidylinositol 3-kinase/Protein Kinase B(LBY24H290002)

Abstract

OBJECTIVE: To investigate the effect of No. 2 Kangxianling decoction (抗纤灵二号方,No. 2 KXLD) on renal tubular injury in renal ischemia/reperfusion injury (RIRI) rats and explore the mechanisms.

METHODS: Male Sprague-Dawley rats were divided into sham group, RIRI group, No. 2 KXLD group, and FG-4592 group. Rats were pretreated with No. 2 KXLD (30 g·kg-1·d-1, i.g.) or FG-4592 (10 mg·kg-1·d-1, i.p.) for 7 d and then subjected to renal I/R. Serum creatinine (Scr) and blood urine nitrogen (BUN) were tested after I/R. Periodic acid-Schiff staining and tubular injury biomarkers were measured. Hypoxia-inducible factor (HIF), inflammatory response, and B-cell lymphoma 2/Bcl-2-associated X protein/caspase-9/3 (Bcl-2/Bax/caspase-9/3) signaling were determined. We used human kidney 2 (HK-2) cells in a hypoxia/reoxygenation (H/R) model to verify the study.

RESULTS: No. 2 KXLD significantly decreased the levels of Scr by 22.4% and BUN by 19.7% at 48 h after I/R and improved the renal pathological changes in RIRI rats. No. 2 KXLD attenuated the expression of kidney injury molecule-1, neutrophil-gelatinase-associated lipocalin, and tissue inhibitor of metalloproteinase-2 in RIRI rats and H/R-induced HK-2 cells (P < 0.05). Both in vivo and in vitro studies demonstrated that No. 2 KXLD increased hypoxia-inducible factor, erythropoietin, and heme oxygenase 1 levels, suppressed tumor necrosis factor-α and interleukin-6 expressions, and boosted Bcl-2/Bax/caspase-9/3 pathway.

CONCLUSIONS: No. 2 KXLD might have therapeutic potential on RIRI by inhibiting HIF-mediated inflammation and apoptosis, which provides a theoretical basis for the treatment of patients with renal tubulointerstitial injury.

Cite this article

YU Kena , ZHONG Liping , LIN Xiaomeng , CHEN Jian , HE Liqun , CAI Xudong . No. 2 Kangxianling decoction (抗纤灵二号方) protects against renal ischemia/reperfusion injury by hypoxia-inducible factor activation[J]. Journal of Traditional Chinese Medicine, 2026 , 46(2) : 306 -315 . DOI: 10.19852/j.cnki.jtcm.2026.02.004

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