Effect of penehyclidine hydrochloride pretreatment on Nrf2/HO-1 signaling pathway in renal tissues of rats with rhabdomyolysis-induced acute kidney injury

Abstract

Objective To investigate the effect of penehyclidine hydrochloride (PHC) pretreatment on nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway in renal tissues of rats with rhabdomyolysis-induced acute kidney injury (AKI). Methods Thirty-six pathogen-free male Sprague-Dawley rats, weighing 200-220 g, were assigned into 3 groups (n=12 each) using a random number table: control group (group C), group AKI and PHC pretreatment group(group PHC). Rhabdomyolysis was induced by intramuscular injection of 50% glycerol 10 ml/kg in bilateral hindlimbs.PHC 0.2 mg/kg was injected intraperitoneally at 30 min before glycerol was injected intramuscularly in group PHC.At 1 and 6 h after glycerol injection, serum was collected for determination of blood urea nitrogen(BUN) and creatinine(Cr) concentrations, and bilateral kidneys were harvested for pathological examination and for determination of HO-1 activity and expression of Nrf2 mRNA and HO-1 mRNA (by quantitative real-time polymerase chain reaction), Nrf2 in nucleoprotein and total protein and HO-1 in total protein in renal tissues (by Western blot). The damage to the renal tubules was scored. Results Compared with group C, the BUN and Cr concentrations in serum and renal tubular damage scores were significantly increased, the expression of Nrf2 in nucleoprotein and total protein and HO-1 in total protein was significantly up-regulated, and HO-1 activity was significantly increased in AKI and PHC groups, the expression of HO-1 mRNA was significantly up-regulated in group AKI, and the expression of Nrf2 mRNA and HO-1 mRNA was significantly up-regulated in group PHC (P<0.01 or 0.05). Compared with group AKI, the BUN and Cr concentrations in serum and renal tubular damage scores were significantly decreased, the expression of Nrf2 in nucleoprotein and total protein and HO-1 in total protein was significantly up-regulated, and HO-1 activity was significantly increased in group PHC (P<0.01 or 0.05). Conclusion The mechanism by which PHC pretreatment attenuates rhabdomyolysis-induced AKI may be related to activation of Nrf2/HO-1 signaling pathway in renal tissues of rats. Key words: Penehyclidine hydrochloride; Rhabdomyolysis; Kidney; Nuclear factor erythroid 2-related factor 2; Heme oxygenase-1