隐丹参酮对慢性皮质酮注射诱导抑郁小鼠的干预作用

Intervention of cryptotanshinone on depression induced by chronic corticosterone injection in mice

目的观察隐丹参酮对慢性皮质酮(CORT)注射诱导抑郁小鼠的干预作用。方法选取60只雄性SPF级KM小鼠,按随机数字表法将其分为隐丹参酮低剂量组(10 mg/kg)、隐丹参酮中剂量组(20 mg/kg)、隐丹参酮高剂量组(40 mg/kg)、氟西汀组(20 mg/kg)、正常对照组(等量生理盐水)、模型组(等量生理盐水),每组10只。除正常对照组外,其余各组通过连续注射CORT(20 mg/kg)建立抑郁模型,造模同时给药。连续给药21 d后,观察隐丹参酮对小鼠体重增加值、糖水消耗比的影响,通过强迫游泳实验、旷场实验、水迷宫测试进行行为学评价,测定小鼠血清CORT、促肾上腺皮质激素(ACTH)水平及海马、前额叶皮质中脑源性神经营养因子(BDNF)水平。结果模型组体重增加值、糖水消耗比、BDNF含量低于正常对照组,不动时间、中央格停留时间、逃避潜伏期长于正常对照组,水平穿越格数、直立次数、修饰次数少于正常对照组,目标象限停留时间、站台周围活动路程短于正常对照组,CORT和ACTH含量高于正常对照组,差异有统计学意义(P<0.05或P<0.01)。隐丹参酮各剂量组体重增加值高于模型组,中央格停留时间短于模型组,水平穿越格数、修饰次数多于模型组,CORT、ACTH水平低于模型组,差异有统计学意义(P<0.05或P<0.01)。隐丹参酮中、高剂量组糖水消耗比高于模型组,不动时间短于模型组,中央格停留时间短于隐丹参酮低剂量组,直立次数多于模型组和隐丹参酮低剂量组,水平穿越格数、修饰次数多于隐丹参酮低剂量组,逃避潜伏期短于模型组,目标象限停留时间、站台周围活动路程长于模型组,CORT、ACTH水平低于隐丹参酮低剂量组,BDNF含量高于模型组和隐丹参酮低剂量组,差异有统计学意义(P<0.05或P<0.01)。隐丹参酮高剂量组逃避潜伏期短于隐丹参酮低、中剂量组,CORT水平低于隐丹参酮中剂量组,海马BDNF含量高于隐丹参酮中剂量组,差异有统计学意义(P<0.05或P<0.01)。结论隐丹参酮可改善CORT诱导小鼠的抑郁样行为,中、高剂量组效果较为明显,其机制可能与调节下丘脑-垂体-肾上腺轴功能、上调脑内BDNF表达水平有关。

Objective To observe the intervention of cryptotanshinone on depression induced by chronic corticosterone(CORT)injection in mice.Methods Sixty male SPF KM mice were selected.According to random number table method,they were divided into cryptotanshinone low-dose group(10 mg/kg),cryptotanshinone medium-dose group(20 mg/kg),cryptotanshinone high-dose group(40 mg/kg),Fluoxetine group(20 mg/kg),normal control group(equal amount of normal saline),and model group(equal amount of normal saline),with ten mice in each group.Except for normal control group,the depression model was established by continuous injection of CORT(20 mg/kg)in other groups,and the model was established at the same time.After 21 days of continuous administration,the effects of cryptotanshinone on body weight gain,sugar water consumption ratio of mice were observed.Behavioral evaluation was conducted by forced swimming test,open field test and water maze test.Serum levels of CORT,adrenocorticotropic hormone(ACTH),and brain-derived neurotrophic factor(BDNF)in hippocampus and prefrontal cortex were determined.Results In model group,the weight gain,sugar water consumption ratio,and BDNF content were lower than those in normal control group,the immobility time,central lattice residence time,and escape latency were longer than those of the normal control group,the number of horizontal crossing lattice,upright times,and modification times were less than those of normal control group,the stay time of the target quadrant and the movement distance around the platform were shorter than those of the normal control group,the contents of CORT and ACTH were higher than those of normal control group,and the differences were statistically significant(P<0.05 or P<0.01).In cryptotanshinone dose groups,the weight gain was higher than that of the model group,the central lattice residence time was shorter than that of model group,the number of horizontal crossing lattice and modification times were more than those of model group,and the levels of CORT and ACTH were lower than that of model group,the differences were statistically significant(P<0.05 or P<0.01).In cryptotanshinone medium-dose and high-dose groups,the sugar water consumption ratio was higher than that of model group,the immobility time was shorter than the model group,the center lattice residence time was shorter than the cryptotanshinone low-dose group,and the upright times were more than the model group and the cryptotanshinone low-dose group,the number of horizontal crossing lattice and the modifications times were more than those of cryptotanshinone low-dose group,the escape latency was shorter than that of the model group,the stay time of the target quadrant and the movement distance around the platform were longer than those of the model group,levels of CORT and ACTH were lower than those of cryptotanshinone low-dose group,and the content of BDNF was higher than that of the model group and the cryptotanshinone low-dose group,with statistical significances(P<0.05 or P<0.01).The escape latency in the cryptotanshinone high-dose group was shorter than that in the cryptotanshinone low and medium dose groups,the level of CORT was lower than that in the cryptotanshinone medium-dose group,and the content of BDNF in hippocampus was higher than that in the cryptotanshinone medium-dose group,with statistical significances(P<0.05 or P<0.01).Conclusion Cryptotanshinone can improve the depression-like behavior of CORT-induced mice,and the effect is more obvious in the medium-dose and high-dose groups.The mechanism may be related to the regulation of hypothalamic-pituitary-adrenal axis function and the up-regulation of BDNF expression level in brain.