| 葛根素对围绝经期抑郁症模型小鼠神经元凋亡的影响及机制研究 |
| 投稿时间：2016-12-12 修订日期：2016-12-20 点此下载全文 |
| 引用本文：王睿,刘吉成,罗春娟,刘立琨,周丽,张琪,张晓杰.葛根素对围绝经期抑郁症模型小鼠神经元凋亡的影响及机制研究[J].医学研究杂志,2017,46(8):121-125 |
| DOI：
10.11969/j.issn.1673-548X.2017.08.030 |
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| 基金项目:黑龙江省齐齐哈尔市科技攻关计划项目（SFGG-2015061） |
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| 中文摘要:目的 探讨葛根素对围绝经期抑郁症模型小鼠神经元凋亡及相关凋亡蛋白表达影响。方法 清洁级昆明小鼠适应性饲养1周以适应环境。旷场实验（OFT）筛选后，随机分为假手术组、围绝经期抑郁症模型组、氟西汀（3mg/kg）+雌激素（0.15mg/kg）组、葛根素组（92mg/kg），每组10只。采用小鼠双侧卵巢切除（OVX）联合慢性不可预知性温和应激（CUMS）法建立围绝经期抑郁症动物模型。各给药组于每日应激前1h灌胃给药，其余各组给予等体积生理盐水，共计21天。观察小鼠动情周期变化，测定行为学变化，尼氏染色及电镜观察海马神经元凋亡情况，Western blot法测定Bcl-2、Bax、caspase-3及caspase-9蛋白表达。结果 除假手术组外，各OVX组小鼠连续7天内连续监测未见动情周期变化，证明去势成功。与假手术组比较，围绝经期抑郁症模型组小鼠呈现抑郁样行为，表现为自发活动及探索行为减少、行为绝望时间增加，海马神经元损伤、数量减少、尼氏体减少及早期凋亡变化，Bcl-2蛋白表达减少而Bax、caspase-3及caspase-9蛋白表达增加（P<0.01或P<0.05）。与围绝经期抑郁症模型组比较，给予葛根素治疗后，可逆转小鼠抑郁样行为，表现为自发活动及探索行为增加，减轻海马神经元损伤及凋亡，增加Bcl-2蛋白表达，减少Bax、caspase-3及caspase-9蛋白表达（P<0.01或P<0.05）。结论 葛根素具有抑制围绝经期抑郁症模型小鼠神经元损伤及凋亡作用，其作用机制可能与调控凋亡信号通路相关蛋白Bcl-2、Bax、caspase-3及caspase-9蛋白表达异常有关。 |
| 中文关键词:葛根素 围绝经期抑郁症 雌激素 凋亡 |
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| Effect and Mechanism of Puerarin on Neuron Apoptosis in Mice Model of Perimenopausal Depression |
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| Abstract:Objective To investigate the effects of related protein expression and neuron apoptosis of puerarin on mice model of perimenopausal depression. Methods The Kunming mice were randomly devided into the sham group,the model group,the fluoxetine(3mg/kg)+estrogen group(0.15mg/kg) and the puerarin group(92mg/kg),10 mice in each group.In this study,we used OVX+CUMS mice as the animal model of perimenopausal depression.The mice were gavaged with or phsiological saline one hour before the daily stress for 21 days.The stages of the estrous cycle were determined by vaginal smears.The mice were tested by open field test(OFT) and foece swimming test(FST) for depressive-like behavior.The morphological and apoptosis change in hippocampal neurons were detected by light microscope and electron microscope.The expressions of Bcl-2,Bax,caspase-3 and caspase-9 were detected by Western blot. Results All of the OVX mice were in the diestrou stage of the estrous cycle.Compared with the sham group,the perimenopausal depression model mice were showed depressive-like behavior.It was characterized as the increasing score in horizontal and locomotor activity in OFT and the increasing despair time in FST(P<0.01 or P<0.05).The morphological damage of hippocampus neurons were observed.The hippocampal neurons were damaged. The number of neurons and nissl bodies was reduced. The neurons were showed apoptosis change.The protein expression of Bcl-2 was decreased but the Bax,caspase-3 and caspase-9 were increased(P<0.01or P<0.05).Compared with the perimenopausal depression model group,if we gave them the puerarin,the depressive-like behavior was reversioned.It was characterized as spontaneous activitives and exploratory behaviors were increased and behavioral despair time were decreased.The injury and apoptosis in hippocamps neurons were alleviated. The protein expression of Bcl-2 was increased but the Bax,caspase-3,and caspase-9 were decreased(P<0.01 or P<0.05). Conclusion Puerarin has effect on the neurons injury and apoptosis in mice model of perimenopausal depression.The mechanism may be related to the protein expression of Bcl-2,Bax,caspase-3 and caspase-9 were abnormal in apoptosis signaling pathways. |
| keywords:Puerarin Perimenopausal depression Estrogen Apoptosis |
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