No. 2 Kangxianling decoction protects against renal ischemia/reperfusion injury by hypoxia-inducible factor activation.

Objective: To investigate the effect of No. 2 Kangxianling decoction (，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.