SA4503对抑郁大鼠海马CREB及BDNF的影响

Effects of SA4503 on CREB and BDNF in the hippocampus in rats with depression

目的观察SA4503对抑郁大鼠海马环磷酸腺苷应答元件结合蛋白(CREB)及脑源性神经营养因子(BDNF)的影响。方法雄性Wistar大鼠32只随机均分为对照组(C组)和三个剂量SA4503组(K1-3组)。实验药物干预前1d,大鼠强迫游泳15min建立抑郁大鼠模型。药物干预当日,分别腹腔注射1ml等容量的生理盐水(C组)、SA4503 2.5mg/kg(S1组)、5mg/kg(S2组)、10mg/kg(S3组)。给药30min后将大鼠再次行强迫游泳实验5min,记录其不动时间。随后取海马组织测定CREB及BDNF含量。结果与C组相比,S1-3组呈剂量依赖性地减少大鼠强迫游泳不动时间及增加海马CREB和BDNF表达(P<0.05)。结论 SA4503对大鼠的抗抑郁作用可能与前额皮层CREB及BDNF表达上调有关。

Objective To observe the effects of SA4503 on cAMP-response element binding protein（CREB） and brain-derived neurophic factor（BDNF） in the hippocampus in rats with depression.Methods Fourty-two male Wistar rats were equally randomized into 4 groups of S1（intraperitoneal injection of SA4503 2.5 mg/kg）,S2（intraperitoneal injection of SA4503 5 mg/kg）,S3（intraperitoneal injection of SA4503 10 mg/kg） and C（intraperitoneal injection of normalsaline）.Depression model of rats was established by being forced to swim for 15 min on the 1st day.The drugs were injected intraperitoneally on the 2nd day and the rats underwent forced swimming test（FST） at 30 min after injection of drugs.The immobility time of the rats during FST was recorded.The hippocampus was harvested for the determination of CREB and BDNF levels after FST.ResultsCompared to group C,the immobility time of the rats during FST was shortened and the expressions of CREB and BDNF in the hippocampus were increased dose-dependently in groups of S1,S2 and S3（P0.05）.Conclusion The anti-depression effect of SA4503 may be related to up-regulating expressions of CREB and BDNF in the hippocampus in rats.