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