摘要
目的探讨颐脑解郁复方治疗卒中后抑郁的可能作用机制。方法将216只SD大鼠随机分为空白组、假手术组、卒中组、卒中后抑郁组、西药组和中药组各36只(每组2、4、8周各12只)。空白组不干预,假手术组不插入线栓,卒中组仅行大脑中动脉阻塞术,卒中后抑郁组、西药组、中药组在卒中后1周应用慢性束缚应激复合单笼饲养的方法制备卒中后抑郁大鼠模型。自脑卒中造模开始,西药组给予盐酸氟西汀胶囊2.33 mg/(kg·d)灌胃,中药组给予颐脑解郁复方9.92 g/(kg·d)灌胃,其余各组大鼠灌胃3 ml蒸馏水,均每日1次。分别于卒中后2、4、8周,采用实时定量PCR技术检测大鼠左侧海马Notch通路上受体Notch1、转录因子Hes1基因表达水平;采用免疫组织化学法检测海马齿状回神经元核抗原(Neu N)、胶质原纤维酸性蛋白(GFAP)表达水平。结果在2、4、8周时,卒中后抑郁组较空白组大鼠海马齿状回Neu N蛋白降低,GFAP蛋白升高(P<0.05或P<0.01);2、4周时中药组和西药组Neu N蛋白较卒中后抑郁组升高,2、4、8周时GFAP蛋白降低(P<0.05或P<0.01)。在2周时,各组大鼠海马齿状回区Notch1、Hes1基因表达差异无统计学意义(P>0.05);4周时中药组大鼠海马齿状回区Notch1、Hes1基因表达较卒中后抑郁组升高(P<0.01);8周时卒中后抑郁组大鼠Notch1、Hes1基因表达与中药组差异无统计学意义(P>0.05)。结论颐脑解郁复方可能通过上调Notch信号通路上Notch1、Hes1基因表达,增加海马齿状回神经元数量,降低星形胶质细胞数量,从而治疗脑卒中后抑郁。
Objective To explore the potential mechanism of Yirtao Xieyu Compound （颐脑解郁复方, YJC） in treating post-stroke depression. Methods A total of 216 Sprague Dawley rats were randomized into blank group, sham operation group, stroke group, post-stroke depression group, Western medicine （WM） group and Chinese med- icine （CM） group, with 36 rats in each group （12 rats respectively in the 2nd, 4th and 8th week）. The blank group was not intervened, the sham operation group was not given middle cerebral artery occlusion （MCAO） , the stroke group was given MCAO alone, while chronic restraint stress combined single-cage feeding was used to build post-stroke depression rat model one week after stroke in the post-stroke depression group, WM group and CM group. From the beginning of the modeling, WM group was given 2.33 rag/（ kg ~ d） of fluoxetine hydrochloride capsule orally, CM group was given 9.92 g/（ kg ~ d） of YJC orally, while other groups were given 3 ml of distilled water by gavage. All interventions were given once a day. At the 2nd, 4th and 8th weeks after stroke, real-time quantitative PCR was used to detect the expressions of Notchl and Hesl genes in the left hippocampus, and immunohistochemistry was used to detect the expressions of nuclear antigen （NeuN） and glial fibrillary acidic protein （GFAP）. Results At the 2nd, 4th and 8th weeks, NeuN protein in the post-stroke depression group was lower, while GFAP protein higher than those in the blank group （P 〈0.05 or P 〈0. 01 ） ; at the 2nd and 4th weeks, NeuN protein in CM group and WM group were higher, while GFAP lower at the 2nd, 4th and 8th weeks than that in post-stroke depression group （ P 〈 0. 05 or P 〈0. 01 ）. At the 2nd week, there was no significant difference in the expression of Notchl and Hesl genes in hipp- ocampal dentate gyms among each group （P 〉 0. 05）. At the 4th week, the expressions of Notchl and Hesl genes in hippocampal dentate gyms of rats in CM group was higher than those in post-stroke depression group （P 〈 0. 01 ）. There were no significant differences in the expressions of Notchl and Hesl between CM group and post-stroke depres- sion group at the 8th week （ P 〉 0.05 ）. Conclusion YJC may treat post-stroke depression by up-regulating the Notchl and Hesl gene expressions in the Notch signaling pathway, increasing the number of neurons in the dentate gyms and decreasing the number of astrocytes in the hippocampus.
出处
《中医杂志》
CSCD
北大核心
2018年第4期333-338,共6页
Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81673930)
北京市自然科学基金(7142100)
北京中医药大学2017年度基本科研业务费项目(2017-JYB-XS-121)
关键词
卒中后抑郁
颐脑解郁复方
神经发生
NOTCH信号通路
post-stroke depression
Yinao Xieyu Compound （颐脑解郁复方）
neurogenesis
Notch signaling pathway
