黄连素对Aβ诱导的大鼠抑郁行为的缓解作用及其相关机制  

Effects of berberine on Aβ-induced depression and its possible mechanism

作　　者：牛玉虎[1] 郭国英[1] 弓韬[1] 张栋[1] 王惠珍[1] NIU Yuhu GUO Guoying GONG Tao ZHANG Dong WANG Huizhen(Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China)

机构地区：[1]山西医科大学生物化学与分子生物学实验室,太原030001

出　　处：《山西医科大学学报》2017年第6期519-525,共7页Journal of Shanxi Medical University

摘　　要：目的探讨黄连素侧脑室注射对β淀粉样蛋白引起大鼠的抑郁焦虑行为的缓解作用及其可能机制。方法 60只大鼠随机分为对照组、Aβ组、低剂量黄连素治疗组、高剂量黄连素治疗组和氟西汀阳性对照组,每组12只,行为学试验检测各组大鼠抑郁焦虑行为,ELISA测定血浆皮质醇和促肾上腺皮质素含量。体外培养的原代星形胶质细胞分为对照组、Aβ组、低剂量黄连素组、高剂量黄连素组和氟西汀阳性对照组,检测各组细胞上清液脑源性神经营养因子,神经生长因子及胶质源性神经营养因子的含量。结果悬尾实验与强制游泳实验显示,Aβ组比对照组大鼠的活动时间显著减少(P<0.001),高剂量黄连素治疗组比Aβ组活动时间显著延长(P<0.05),低剂量组与Aβ组差异并无统计学意义。应激状况下Aβ组血浆皮质醇与促肾上腺皮质激素相较于对照组明显升高(P<0.01),而正常情况下两种激素在各组差异无统计学意义。与Aβ组相比,黄连素治疗组两种激素水平下降(P<0.01)。细胞上清液检测显示,与对照组相比,Aβ组的脑源性神经营养因子、神经生长因子及胶质源性神经营养因子的分泌水平明显减低(P<0.001),与Aβ组相比,高剂量黄连素治疗组中三种神经营养因子分泌水平均显著增加(P<0.05)。结论黄连素能够显著缓解β淀粉样蛋白引起的抑郁焦虑情绪,这种缓解作用可能与其对应激性激素的调节以及对胶质细胞神经营养因子分泌的促进作用有关。Objective To investigate the antidepressant and anti-anxiety effects of berberine in Aβ-induced depression rats and its pos- sible mechanism. Methods Sixty rats were randomized into five groups （ n = 12 in each group） ：control group, Aβ group, low dose berberine group, high dose berberine group, and fluoxetine group. Behavioral tests were performed to determine the depressive and anxie- ty behaviors of rats in each group. Plasma levels of corticosterone and adrenocorticotropic hormone were detected by ELISA. Astrocytes were divided into five groups：control group, Aβ group, low dose berberine group, high dose berberine group and fluoxetine group. The concentrations of brain-derived neurotrophic factor（BDNF） ,nerve growth factor（NGF） and glia-derived neurotrophic factor（GDNF） in cell culture fluids were analyzed by ELISA. Results ①The tail suspension and forced swim tests indicated that the mobility time sig- nificantly decreased in Aβ group compared with control group （P 〈 O. 001 ）. While the mobility time was significantly prolonged in high dose berberine group compared with Aβ group（P 〈 0.05 ）. ②ELISA assay for detecting the stress hormone in plasma showed that com- pared with control group, the production of cortisol and ACTH increased under the stress condition in Aβ group （ P 〈 0.001 ）, but no sig- nificant difference was found among different groups under the normal condition. Additionally, compared with Aβ group, the secretion of two stress hormones decreased under the stress condition in berberine groups （P 〈 O. 01 ）. ③Compared with control group, the produc- tion of BDNF, NGF and GDNF decreased in Aβ group （ P 〈 O. 001 ）. Compared with AI3 group, the secretion of BDNF, NGF and GDNF significantly increased in high dose berberine group （ P 〈 0.05 ）. Conclusion Berberine can alleviate the depressive and anxiety symptoms induced by A[3. The improved regulation on stress hormone and promotion effects on production of neurotrophins might be t

关 键 词：黄连素 β淀粉样蛋白 抑郁焦虑行为 脑源性神经营养因子 神经生长因子 胶质源性神经营养因子 阿尔兹海默病 

分 类 号：R749.1[医药卫生—神经病学与精神病学]