DL-3-n-butylphthalide improved physical and learning and memory performance of rodents exposed to acute and chronic hypobaric hypoxia

Background: Studies revealed the protective effect of DL-3-n-butylphthalide (NBP) against ischemic hypoxia diseases. However, the role of NBP in animals with hypobaric hypoxia is elusive. This study investigated the effect of NBP on animals with acute and chronic hypobaric hypoxia. Methods: SD rats and Kunming mice administrated with NBP ( 90, 180 and 360 mg/kg for mice, 60, 120, and 240 mg/kg for rats and 90, 180 and 360 mg/kg for mice 60, 120, and 240 mg/kg for rats ) were placed located in 10,000 m hypobaric hypoxia chamber. And survival analysis of animals implied that NBP could significantly improve and survival percent at 30 min were analyzed . Then, drug treated animals rats (mice) were evaluated for exhaustive exhausted time and exhaustive exhausted distance in forced exercise wheel-track treadmill and treadmill running and motor-driven wheel-track treadmill experiments at 5,800 m (5,000 m) for 3 or 21 days or 21 days , to evaluate changes of physical functions. Rats were also evaluated for times of active escape , and average time of active escape , time of passive escape, and average time of passive escape in a shuttle-box experiment at 5,800 m for 7 days or 28 days 7 or 28 days , to evaluate changes of cognitive learning and memory function s . ATP level was evaluated measured in the gastrocnemius muscle and maloaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H 2 O 2 ), lactate, and glutathione peroxiase (GSH-Px) measurements and routine blood tests were detected in serum of rats . Results: Survival analysis in 10,000 m indicated NBP could improve hypoxia tolerance ability. Exhaustive Exhausted time for rats (NBP, 120 and 240 mg/kg) and exhaustive exhausted time and distance for mice (NBP, 90 mg/kg) significantly increased under acute hypoxia. And NBP treatment also significantly increased the exhaustive exhausted time for rats under chronic hypoxia. Moreover, NBP of 120 and 240 mg/kg significantly increased the average time s of passive active escape under acute and chronic hypoxia. These results suggested that NBP could improve physical and cognitive learning and memory functions under acute and chronic hypobaric hypoxia. Furthermore, the levels of MDA and H 2 O 2 decreased but those of SOD and GSH-Px in serum of rats increased under acute and chronic hypoxia. Furthermore, Additionally, the content of ATP in gastrocnemius muscle significantly increased, while lactate in serum level significantly decreased. The results presented suggested that NBP could regulate redox homeostasis and improve energy metabolism of hypobaric hypoxic rats. Conclusion: NBP could improve physical and cognitive learning and memory functions under acute and chronic hypobaric hypoxia by increasing anti-oxidative capacity and energy supply.