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Objective: To investigate the protective effect of penehvclidine hvdrochloride on ischemia-reperfusion injury in rats. Method: The model of ischemia-reperfusion injury was established in rats through clamping rental pedicles for 50 min followed by reperfusion. A total of 60 Wistar rats were randomly divided into 4 groups including fake surgery group, model group, low PHC dosage group and high dosage penehvclidine hvdrochloride (PHC) group. Seven days before the experiment, rats in fake surgery group and model group were given 10 mL/kg normal saline, while rats in low PHC dosage group and high dosage PHC group were given 200 and 50 mg/kg PHC, respectively. The urine volume, diet volume, Cre, PU, BUN, IL-6, IL-8, TNF-α, NO MDA concentration, SOD and GSH-Px were determined. Results: Compared with rats in model group, decreased urine volume, diet volume, Cre, PU, BUN, IL-6, IL-8, TNF-α, NO MDA concentration and increased SOD and GSH-Px activity could be seen in low PHC dosage group and high dosage PHC group (P<0.05). Conclusions: Administration of PHC before ischemia-reperfusion injury can help protect ischemia-reperfusion injury.