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南京中医药大学 附属医院,南京 210029
[第一作者] 宋珊珊,在读硕士,从事临床中药学研究,E-mail: 402810414@qq.com
*居文政,博士,主任药师,从事中药临床药理学研究,E-mail: wzhju333@163.com
收稿日期:2019-06-13,
网络出版日期:2019-09-11,
纸质出版日期:2020-02-20
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宋珊珊, 孙红, 井汶, 等. 基于雌激素受体通路探讨青娥丸对CUMS大鼠的抗抑郁机制[J]. 中国实验方剂学杂志, 2020,26(4):9-15.
Shan-shan SONG, Hong SUN, Wen JING, et al. Anti-depressant Mechanism of Qing' ewan in CUMS Rats Based on Estrogen Receptor Pathway[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 9-15.
宋珊珊, 孙红, 井汶, 等. 基于雌激素受体通路探讨青娥丸对CUMS大鼠的抗抑郁机制[J]. 中国实验方剂学杂志, 2020,26(4):9-15. DOI: 10.13422/j.cnki.syfjx.20200103.
Shan-shan SONG, Hong SUN, Wen JING, et al. Anti-depressant Mechanism of Qing' ewan in CUMS Rats Based on Estrogen Receptor Pathway[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 9-15. DOI: 10.13422/j.cnki.syfjx.20200103.
目的:
2
研究青娥丸对慢性温和不可预知应激模型(CUMS)大鼠的抗抑郁效果,及其对雌激素受体及相关信号通路的调控作用,探讨青娥丸的抗抑郁机制。
方法:
2
54只SD大鼠建立CUMS抑郁大鼠模型,实验设为正常组、模型组、草酸依他普伦组(6.3 mg·kg
-1
)及青娥丸低、中、高剂量组(1.71,5.13,15.39 g·kg
-1
)。CUMS造模4周后给予各组相应药物治疗2周,采用行为学[糖水消耗实验(SPT),强迫游泳实验(FST),旷场实验(OFT)]评价大鼠抑郁状态;采用蛋白免疫印迹法(Western blot)检测雌激素受体
α
(ER
α
),雌激素受体
β
(ER
β
),脑源性神经营养因子(BDNF)及酪氨酸激酶受体B(TrkB)的蛋白表达水平。
结果:
2
与正常组比较,模型组大鼠的糖水消耗率及旷场得分均下降(
P
<
0.05,
P
<
0.01),游泳不动时间显著延长(
P
<
0.01),同时ER
α
,ER
β
,BDNF和TrkB的蛋白表达水平下降(
P
<
0.05,
P
<
0.01);与模型组比较,各给药组大鼠的行为学表现得到改善,糖水消耗率及旷场得分增加(
P
<
0.05,
P
<
0.01),游泳不动时间减少(
P
<
0.05),同时ER
α
,ER
β
,BDNF和TrkB蛋白的表达明显上调(
P
<
0.05,
P
<
0.01),其中青娥丸中剂量组的调节作用更为显著。
结论:
2
青娥丸可改善CUMS模型大鼠的抑郁样行为,其机制可能与上调ER
α
,ER
β
的表达,激活雌激素受体介导的ER
β
/BDNF/TrkB通路起到神经保护作用有关。
Objective:
2
To study the anti-depressive effect of Qing' ewan in treating chronic unpredictable mild stress (CUMS) in rats
and the regulatory effect on estrogen receptor and estrogen receptor-related signaling pathways
in order to explore its anti-depressive mechanism.
Method:
2
The CUMS model was established. The experiment was divided into normal control group
model group
escitalopram oxalate group (positive control) and Qing' ewan groups (1.71
5.13
15.39 g·kg
-1
). After 4 weeks of modeling
rats were treated with corresponding drugs for 2 weeks. Behavioral evaluation [sucrose preference test (SPT)
forced swimming test (FST)
open field test (OFT)] was conducted to assess if the CUMS model was successful. Western blot was used to analyze the protein expression levels of estrogen receptor
α
(ER
α
)
estrogen receptor
β
(ER
β
)
brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB).
Result:
2
Compared with the normal group
the sucrose consumption rate and the score of OFT in the model group decreased(
P
<
0.05
P
<
0.01)
the immobility time of FST prolonged significantly(
P
<
0.01)
and the protein expression levels of ER
α
ER
β
BDNF and TrkB decreased(
P
<
0.05
P
<
0.01). Compared with the model group
the behavioral performance of the treated group was improved
the sucrose consumption rate and the score of OFT increased(
P
<
0.05
P
<
0.01)
and the immobility time decreased(
P
<
0.05). The protein expressions of ER
α
ER
β
BDNF and TrkB in the treated group were significantly up-regulated(
P
<
0.05
P
<
0.01)
especially the middle-dose Qing' ewan group (5.13 g·kg
-1
).
Conclusion:
2
Qing' ewan can improve depression-like behavior in CUMS rats. Its mechanism may be related to the neuroprotective effect by up-regulating the expressions of ER
α
and ER
β
and activating estrogen receptor-mediated ER
β
/BDNF/TrkB pathways.
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