Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (2): 306-315.DOI: 10.19852/j.cnki.jtcm.2026.02.004
• Original Articles • Previous Articles Next Articles
No. 2 Kangxianling decoction (抗纤灵二号方) protects against renal ischemia/reperfusion injury by hypoxia-inducible factor activation
YU Kena1, ZHONG Liping4, LIN Xiaomeng1, CHEN Jian5, HE Liqun2,3(
), CAI Xudong1()
- 1
Department of Nephrology ,Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University Ningbo 315000, China
2Shanghai University of Traditional Chinese Medicine Shanghai 200120, China
3Department of Nephrology ,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 200013, China
4Department of Nephrology ,Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine Wuhan 430000, China
5Department of Traditional Medicine ,Shanghai Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 200082, China
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Received:2024-11-19Accepted:2025-06-10Online:2026-04-15Published:2026-04-04 -
Contact: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 -
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)
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.
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Figure 1 No. 2 KXLD attenuated the tubular injury in RIRI rats A: PAS staining in kidneys; B: Western blot analysis of renal TIMP-2; C: quantitative analysis of TIMP-2 protein. D: immunofluorescence staining of NGAL (green: NGAL; blue: DAPI); A1: sham group at 24 h after I/R; A2: I/R group at 24 h after I/R; A3: FG-4592 group at 24 h after I/R; A4: No. 2 KXLD group at 24 h after I/R; A5: sham group at 48 h after I/R; A6: I/R group at 48 h after I/R; A7: FG-4592 group at 48 h after I/R; A8: No. 2 KXLD group at 48 h after I/R; D1: sham group; D2: RIRI group; D3: FG-4592 group; D4: No. 2 KXLD group. Sham group: sham surgery; RIRI: renal I/R; FG-4592: FG-4592 + renal I/R, 10 mg·kg-1·d-1; No. 2 KXLD: No. 2 KXLD + renal I/R, 30 g·kg-1·d-1, i.g. TIMP-2: tissue inhibitor of metalloproteinases-2; NGAL: neutrophil gelatinase-associated lipocalin; PAS: periodic acid-schiff; RIRI: renal ischemia/reperfusion injury; No. 2 KXLD: No. 2 Kangxianling decoction; DAPI: 4',6-diamidino-2-phenylindole; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; RT-qPCR: reverse transcription quantitative polymerase chain reaction. Data were analyzed using a one-way analysis of variance test with a post hotc (least significant difference analysis) for comparison of multiple independent sample groups. Data were expressed as mean ± standard deviation (n = 3). a P < 0.01 vs sham group at 24 h after I/R; b P < 0.01 vs sham group at 48 h after I/R; c P < 0.01 vs RIRI group at 24 h after I/R; d P < 0.01 vs RIRI group at 48 h after I/R.
Figure 1 No. 2 KXLD attenuated the tubular injury in RIRI rats A: PAS staining in kidneys; B: Western blot analysis of renal TIMP-2; C: quantitative analysis of TIMP-2 protein. D: immunofluorescence staining of NGAL (green: NGAL; blue: DAPI); A1: sham group at 24 h after I/R; A2: I/R group at 24 h after I/R; A3: FG-4592 group at 24 h after I/R; A4: No. 2 KXLD group at 24 h after I/R; A5: sham group at 48 h after I/R; A6: I/R group at 48 h after I/R; A7: FG-4592 group at 48 h after I/R; A8: No. 2 KXLD group at 48 h after I/R; D1: sham group; D2: RIRI group; D3: FG-4592 group; D4: No. 2 KXLD group. Sham group: sham surgery; RIRI: renal I/R; FG-4592: FG-4592 + renal I/R, 10 mg·kg-1·d-1; No. 2 KXLD: No. 2 KXLD + renal I/R, 30 g·kg-1·d-1, i.g. TIMP-2: tissue inhibitor of metalloproteinases-2; NGAL: neutrophil gelatinase-associated lipocalin; PAS: periodic acid-schiff; RIRI: renal ischemia/reperfusion injury; No. 2 KXLD: No. 2 Kangxianling decoction; DAPI: 4',6-diamidino-2-phenylindole; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; RT-qPCR: reverse transcription quantitative polymerase chain reaction. Data were analyzed using a one-way analysis of variance test with a post hotc (least significant difference analysis) for comparison of multiple independent sample groups. Data were expressed as mean ± standard deviation (n = 3). a P < 0.01 vs sham group at 24 h after I/R; b P < 0.01 vs sham group at 48 h after I/R; c P < 0.01 vs RIRI group at 24 h after I/R; d P < 0.01 vs RIRI group at 48 h after I/R.
Figure 2 Effect of No. 2 KXLD on apoptosis in RIRI rats A: representative images of TUNEL staining at 48 h after I/R (630 × magnification; red: TUNEL; blue: DAPI); B: Western blot analysis of Bcl-2, Bax, caspase-3 in kidneys. C: Western blot analysis of caspase-9, cleaved caspase-9/3 in kidneys. A1: sham group; A2: RIRI group; A3: FG-4592 group; A4: No. 2 KXLD group. Sham group: sham surgery, RIRI: renal I/R, FG-4592: FG-4592 + renal I/R, 10 mg·kg-1·d-1; No. 2 KXLD: No. 2 KXLD + renal I/R, 30 g·kg-1·d-1, i.g. DAPI: 4',6-diamidino-2-phenylindole; RIRI: renal ischemia/reperfusion injury; No. 2 KXLD: No. 2 Kangxianling decoction; Bcl-2: B-cell lymphoma 2; Bax: Bcl-2-associated X protein; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; RT-qPCR: reverse transcription quantitative polymerase chain reaction. Data were expressed as mean ± standard deviation (n = 3). Data were analyzed using a one-way analysis of variance test with a post hotc (least significant difference analysis) for comparison of multiple independent sample groups.
Figure 2 Effect of No. 2 KXLD on apoptosis in RIRI rats A: representative images of TUNEL staining at 48 h after I/R (630 × magnification; red: TUNEL; blue: DAPI); B: Western blot analysis of Bcl-2, Bax, caspase-3 in kidneys. C: Western blot analysis of caspase-9, cleaved caspase-9/3 in kidneys. A1: sham group; A2: RIRI group; A3: FG-4592 group; A4: No. 2 KXLD group. Sham group: sham surgery, RIRI: renal I/R, FG-4592: FG-4592 + renal I/R, 10 mg·kg-1·d-1; No. 2 KXLD: No. 2 KXLD + renal I/R, 30 g·kg-1·d-1, i.g. DAPI: 4',6-diamidino-2-phenylindole; RIRI: renal ischemia/reperfusion injury; No. 2 KXLD: No. 2 Kangxianling decoction; Bcl-2: B-cell lymphoma 2; Bax: Bcl-2-associated X protein; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; RT-qPCR: reverse transcription quantitative polymerase chain reaction. Data were expressed as mean ± standard deviation (n = 3). Data were analyzed using a one-way analysis of variance test with a post hotc (least significant difference analysis) for comparison of multiple independent sample groups.
Figure 3 No. 2 KXLD treatment reduced the injury of H/R-induced HK-2 cells by activating HIF activation A: representative images of HK-2 cells in each group (× 200); B: CCK-8 assay was used to analyze the cell viability of HK-2 cells; C: RT-qPCR analyses demonstrated a marked reduction of HIF-1ɑ expression in si-HIF-1ɑ HK-2 cells; D: Western blot analysis of NGAL and TIMP-2 in cells; E: Western blot analysis of HIF-1α, EPO and HO-1 in cells; F: immunofluorescence staining results of KIM-1 in HK-2 cells (400 ×; red: KIM-1; blue: DAPI). A1, F1: control group; A2, F2: H/R group; A3, F3: blank serum group; A4, F4: FG-4592 group; A5, F5: si-HIF-1α + No. 2 KXLD group; A6, F6: No. 2 KXLD group. Control group: normal culture; H/R group: H/R; blank serum group: H/R + blank serum; FG-4592: H/R + FG4592, 10 μg/mL; si- HIF-1α + No. 2 KXLD group: si-HIF-1α + H/R + 25% No. 2 KXLD; No. 2 KXLD group: H/R + 25% No. 2 KXLD. No. 2 KXLD: No. 2 Kangxianling decoction; H/R: hypoxia/reoxygenation; NGAL: neutrophil gelatinase-associated lipocalin; KIM-1: kidney injury molecule-1; TIMP-2: tissue inhibitor of metalloproteinases-2; HIF-1α: hypoxia-inducible factor; EPO: erythropoietin; HO-1: heme oxygenase 1; RT-qPCR: reverse transcription quantitative polymerase chain reaction; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; DAPI: 4',6-diamidino-2-phenylindole; CCK-8: cell counting kit-8. Data were expressed as mean ± standard deviation (n = 3). aP < 0.01 vs control group; bP < 0.01 vs H/R group; cP < 0.01 vs si-NC group.
Figure 3 No. 2 KXLD treatment reduced the injury of H/R-induced HK-2 cells by activating HIF activation A: representative images of HK-2 cells in each group (× 200); B: CCK-8 assay was used to analyze the cell viability of HK-2 cells; C: RT-qPCR analyses demonstrated a marked reduction of HIF-1ɑ expression in si-HIF-1ɑ HK-2 cells; D: Western blot analysis of NGAL and TIMP-2 in cells; E: Western blot analysis of HIF-1α, EPO and HO-1 in cells; F: immunofluorescence staining results of KIM-1 in HK-2 cells (400 ×; red: KIM-1; blue: DAPI). A1, F1: control group; A2, F2: H/R group; A3, F3: blank serum group; A4, F4: FG-4592 group; A5, F5: si-HIF-1α + No. 2 KXLD group; A6, F6: No. 2 KXLD group. Control group: normal culture; H/R group: H/R; blank serum group: H/R + blank serum; FG-4592: H/R + FG4592, 10 μg/mL; si- HIF-1α + No. 2 KXLD group: si-HIF-1α + H/R + 25% No. 2 KXLD; No. 2 KXLD group: H/R + 25% No. 2 KXLD. No. 2 KXLD: No. 2 Kangxianling decoction; H/R: hypoxia/reoxygenation; NGAL: neutrophil gelatinase-associated lipocalin; KIM-1: kidney injury molecule-1; TIMP-2: tissue inhibitor of metalloproteinases-2; HIF-1α: hypoxia-inducible factor; EPO: erythropoietin; HO-1: heme oxygenase 1; RT-qPCR: reverse transcription quantitative polymerase chain reaction; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; DAPI: 4',6-diamidino-2-phenylindole; CCK-8: cell counting kit-8. Data were expressed as mean ± standard deviation (n = 3). aP < 0.01 vs control group; bP < 0.01 vs H/R group; cP < 0.01 vs si-NC group.
Figure 4 Inflammation and apoptosis were suppressed by No. 2 KXLD in H/R-induced HK-2 cells A: Western blot analysis of Bcl-2, Bax, caspase-3 in cells; B: Western blot analysis of caspase-9, cleaved caspase-9/3 in cells; C: representative immunohistochemistry staining of TNF-α and IL-6 in HK-2 cells (×200); C1: TNF-α in sham group; C2: TNF-α expression in H/R group; C3: TNF-α expression in blank serum group; C4: TNF-α expression in FG-4592 group; C5: TNF-α expression in si-HIF-1α + No. 2 KXLD group; C6: TNF-α expression in No. 2 KXLD group; C7: IL-6 expression in sham group; C8: IL-6 expression in H/R group; C9: IL-6 expression in blank serum group; C10: IL-6 expression in FG-4592 group; C11: IL-6 expression in si-HIF-1α + No. 2 KXLD group; C12: IL-6 expression in No. 2 KXLD group. Control group: normal culture; H/R group: H/R; blank serum group: H/R + blank serum; FG-4592: H/R + FG4592, 10 μg/mL; si-HIF-1α + No. 2 KXLD group: si- HIF-1α + H/R + 25% No. 2 KXLD; No. 2 KXLD group: H/R + 25% No. 2 KXLD. No. 2 KXLD: No. 2 Kangxianling decoction; H/R: hypoxia/reoxygenation; Bcl-2: B-cell lymphoma 2; Bax: Bcl-2-associated X protein; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; RT-qPCR: reverse transcription quantitative polymerase chain reaction. Data were expressed as mean ± standard deviation (n = 3).
Figure 4 Inflammation and apoptosis were suppressed by No. 2 KXLD in H/R-induced HK-2 cells A: Western blot analysis of Bcl-2, Bax, caspase-3 in cells; B: Western blot analysis of caspase-9, cleaved caspase-9/3 in cells; C: representative immunohistochemistry staining of TNF-α and IL-6 in HK-2 cells (×200); C1: TNF-α in sham group; C2: TNF-α expression in H/R group; C3: TNF-α expression in blank serum group; C4: TNF-α expression in FG-4592 group; C5: TNF-α expression in si-HIF-1α + No. 2 KXLD group; C6: TNF-α expression in No. 2 KXLD group; C7: IL-6 expression in sham group; C8: IL-6 expression in H/R group; C9: IL-6 expression in blank serum group; C10: IL-6 expression in FG-4592 group; C11: IL-6 expression in si-HIF-1α + No. 2 KXLD group; C12: IL-6 expression in No. 2 KXLD group. Control group: normal culture; H/R group: H/R; blank serum group: H/R + blank serum; FG-4592: H/R + FG4592, 10 μg/mL; si-HIF-1α + No. 2 KXLD group: si- HIF-1α + H/R + 25% No. 2 KXLD; No. 2 KXLD group: H/R + 25% No. 2 KXLD. No. 2 KXLD: No. 2 Kangxianling decoction; H/R: hypoxia/reoxygenation; Bcl-2: B-cell lymphoma 2; Bax: Bcl-2-associated X protein; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; RT-qPCR: reverse transcription quantitative polymerase chain reaction. Data were expressed as mean ± standard deviation (n = 3).
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