中国临床药理学杂志

艾司氯胺酮通过调控TREK-1影响BDNF/TrkB通路改善小鼠产后抑郁的研究

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蒋飞 , 朱吉

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(9): 1284-1292

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (9) : 1284 -1292

艾司氯胺酮通过调控TREK-1影响BDNF/TrkB通路改善小鼠产后抑郁的研究

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蒋飞, 朱吉

作者信息

常州市妇幼保健院药学部，江苏常州 213000

通讯作者:

朱吉，副主任药师 MP: 15961206898 E-mail: 13606120542@163.com

作者简介:

蒋飞（1986-），女，主管药师，主要从事药学方面的工作和研究

Research of esketamine alleviating postpartum depression in mice through regulating TREK-1 to modulate the BDNF/TrkB pathway

Fei JIANG, Ji ZHU

Affiliations

Department of Pharmacy, Changzhou Maternal and Child Health Care Hospital, Changzhou 213000, Jiangsu Province, China

出版时间: 2026-05-17 doi: 10.13699/j.cnki.1001-6821.2026.09.014

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摘要

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目的

探讨艾司氯胺酮（Esk）通过调控双孔钾通道相关蛋白（TWIK）相关钾离子通道1（TREK-1）激活脑源性神经营养因子（BDNF）/酪氨酸蛋白激酶受体B（TrkB）通路对小鼠产后抑郁（PPD）样行为的作用。

方法

将50只C57BL/6J妊娠小鼠随机分为空白组、模型组、实验组、oe-NC组及oe-TREK-1组，每组10只。用慢性温和不可预知刺激（CUMS）法诱导妊娠小鼠建立PPD模型，空白组不建模，给予等量生理盐水；模型组经CUMS造模后给予等量生理盐水；实验组造模后腹腔注射Esk（5 mg·kg^-1）；oe-NC组尾静脉注射慢病毒包被的oe-NC后造模并给予Esk；oe-TREK-1组尾静脉注射慢病毒包被的oe-TREK-1后造模并给予Esk。通过糖水偏好实验（SPT）法和尾悬吊实验（TST）法评估小鼠抑郁样行为；用苏木精-伊红（HE）染色法和尼氏（Nissl）染色法评估海马组织病理特征；用实时荧光定量聚合酶链式反应法和蛋白质印迹法检测海马组织中TREK-1的表达情况；用酶联免疫吸附法测定血清性激素表达水平；用免疫组化法检测小胶质细胞标志蛋白表达情况；用蛋白质印迹法检测内质网应激相关蛋白表达；用免疫荧光法检测脑源性神经营养因子（BDNF）和酪氨酸蛋白激酶B（TrkB）相对表达水平。

结果

空白组、模型组、实验组、oe-NC组和oe-TREK-1组小鼠的糖水偏好率分别为（84.74±14.46）%、（19.08±2.86）%、（79.62±12.54）%、（80.15±11.38）%和（52.44±8.15）%，尾悬吊实验不动时间占比分别为（31.16±4.63）%、（75.38±14.62）%、（49.26±8.59）%、（48.97±7.82）%和（62.53±9.24）%；海马组织中TREK-1 mRNA相对表达水平分别为1.00±0.15、2.87±0.45、1.55±0.21、1.56±0.19和2.18±0.36，TREK-1蛋白相对表达水平分别为1.00±0.16、2.75±0.38、1.86±0.27、1.84±0.19和2.44±0.34；血清雌二醇（E2）水平分别为（1 263.55±152.77）、（638.16±78.32）、（985.24±107.48）、（981.67±106.34）和（752.33±116.45）pg·mL^-1，孕酮（P）水平分别为（9.53±1.06）、（3.48±0.59）、（8.54±1.07）、（8.47±1.04）和（5.62±1.02）ng·mL^-1，催乳素（PRL）水平分别为（15.98±2.19）、（29.31±4.62）、（19.25±2.58）、（19.88±2.67）和（23.47±3.46）ng·mL^-1；海马组织Iba-1蛋白相对表达水平分别为1.00±0.16、0.35±0.05、0.87±0.14、0.85±0.13和0.61±0.11，GRP78蛋白相对表达水平分别为1.00±0.17、1.58±0.16、1.17±0.14、1.09±0.18和1.35±0.17，CHOP蛋白相对表达水平分别为1.00±0.14、1.71±0.23、1.13±0.16、1.11±0.12和1.34±0.18，Cleaved casp-12蛋白相对表达水平分别为1.00±0.16、1.45±0.19、1.19±0.13、1.16±0.12和1.38±0.16；BDNF的相对荧光强度分别为1.00±0.16、0.38±0.06、0.84±0.09、0.83±0.11和0.64±0.08，TrkB的相对荧光强度分别为1.00±0.17、0.57±0.09、0.92±0.14、0.91±0.12和0.75±0.11，模型组的上述指标与空白组比较，实验组的上述指标与模型组比较，oe-TREK-1组的上述指标与oe-NC组比较，在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001）。

结论

艾司氯胺酮可以通过抑制TREK-1表达，调节性激素平衡，改善小胶质细胞功能及内质网应激，进而激活BDNF/TrkB通路，最终缓解小鼠产后抑郁样行为。

关键词

艾司氯胺酮 / 产后抑郁症 / 双孔钾通道相关蛋白相关钾离子通道1 / 脑源性神经营养因子/酪氨酸蛋白激酶受体B

Abstract

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Objective

To investigate the mechanism of esketamine (Esk) ameliorating postpartum depression (PPD)-like behaviors in mice by regulating the two pore domain potassium channel (TWIK)-related K⁺ channel 1(TREK-1) to activate the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, and to provide experimental evidence for clarifying the pathogenesis of PPD and developing novel targeted therapeutic strategies.

Methods

A total of 50 C57BL/6J pregnant mice were randomly divided into five groups (n=10 per group): control group, model group, experimental group, oe-NC group and oe-TREK-1 group. A PPD model was established in pregnant mice using the chronic unpredictable mild stress (CUMS) method. The control group was given an equal volume of normal saline; the model group was given normal saline after CUMS modeling; the experimental group was intraperitoneally injected with Esk (5 mg·kg^-1) once daily for 3 weeks after modeling; the oe-NC group was injected with lentivirus-encapsulated oe-NC by the tail vein before modeling and subsequent Esk administration; the oe-TREK-1 group was injected with lentivirus-encapsulated oe-TREK-1 by the tail vein before modeling and subsequent Esk administration. Depressive-like behaviors were evaluated using the sucrose preference test (SPT) and tail suspension test (TST). Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the pathological morphology of hippocampal tissue; real-time fluorescent quantitative polymerase chain reaction and Western blotting were employed to detect the relative expression levels of TREK-1 in hippocampal tissue; enzyme-linked immunosorbent assay was utilized to measure the expression levels of serum sex hormones; immunohistochemistry was adopted to detect the expression of microglial marker proteins; Western blotting was used to determine the relative expression levels of endoplasmic reticulum stress-related proteins; immunofluorescence was applied to detect the relative expression levels of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB).

Results

The sucrose preference rates in the control, model, experimental, oe-NC and oe-TREK-1 groups were (84.74±14.46)%, (19.08±2.86)%, (79.62±12.54)%, (80.15±11.38)% and (52.44±8.15)%, respectively; the immobility time ratios in the tail suspension test were (31.16±4.63)%, (75.38±14.62)%, (49.26±8.59)%, (48.97±7.82)% and (62.53±9.24)%, respectively; the relative expression levels of TREK-1 mRNA in the hippocampal tissues were 1.00±0.15, 2.87±0.45, 1.55±0.21, 1.56±0.19 and 2.18±0.36, respectively; the relative expression levels of TREK-1 protein were 1.00±0.16, 2.75±0.38, 1.86±0.27, 1.84±0.19 and 2.44±0.34, respectively; serum estradiol (E2) levels were (1 263.55±152.77), (638.16±78.32), (985.24±107.48), (981.67±106.34) and (752.33±116.45) pg·mL^-1, respectively; progesterone (P) levels were (9.53±1.06), (3.48±0.59), (8.54±1.07), (8.47±1.04) and (5.62±1.02) ng·mL^-1, respectively; prolactin (PRL) levels were (15.98±2.19), (29.31±4.62), (19.25±2.58), (19.88±2.67) and (23.47±3.46) ng·mL^-1, respectively; the relative expression levels of Iba-1 protein in the hippocampus were 1.00±0.16, 0.35±0.05, 0.87±0.14, 0.85±0.13 and 0.61±0.11, respectively; the relative expression levels of GRP78 protein were 1.00±0.17, 1.58±0.16, 1.17±0.14, 1.09±0.18 and 1.35±0.17, respectively; the relative expression levels of CHOP protein were 1.00±0.14, 1.71±0.23, 1.13±0.16, 1.11±0.12 and 1.34±0.18, respectively; the relative expression levels of Cleaved caspase-12 protein were 1.00±0.16, 1.45±0.19, 1.19±0.13, 1.16±0.12 and 1.38±0.16, respectively; the relative fluorescence intensities of BDNF were 1.00±0.16, 0.38±0.06, 0.84±0.09, 0.83±0.11 and 0.64±0.08, respectively; the relative fluorescence intensities of TrkB were 1.00±0.17, 0.57±0.09, 0.92±0.14, 0.91±0.12 and 0.75±0.11, respectively. Statistically significant differences were observed in the above indicators between the model group and the control group, between the experimental group and the model group, and between the oe-TREK-1 group and the oe-NC group (P<0.05, P<0.01, P<0.001).

Conclusion

Esketamine can alleviate PPD-like behaviors in mice by inhibiting TREK-1 expression, regulating sex hormone balance, improving microglial function and endoplasmic reticulum stress, and thereby activating the BDNF/TrkB pathway.

Key words

esketamine / postpartum depression / two pore domain potassium channel-related K⁺ channel 1 / brain-derived neurotrophic factor/ tropyrosine kinase B

引用本文

蒋飞, 朱吉. 艾司氯胺酮通过调控TREK-1影响BDNF/TrkB通路改善小鼠产后抑郁的研究. 中国临床药理学杂志, 2026 , 42 (9) : 1284 -1292 . DOI: 10.13699/j.cnki.1001-6821.2026.09.014

Fei JIANG, Ji ZHU. Research of esketamine alleviating postpartum depression in mice through regulating TREK-1 to modulate the BDNF/TrkB pathway[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (9) : 1284 -1292 . DOI: 10.13699/j.cnki.1001-6821.2026.09.014

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2026年第42卷第9期

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doi: 10.13699/j.cnki.1001-6821.2026.09.014

接收时间：2026-01-30
首发时间：2026-08-06
出版时间：2026-05-17

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收稿日期：2026-01-30

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作者信息

常州市妇幼保健院药学部，江苏常州 213000

通讯作者:

朱吉，副主任药师 MP: 15961206898 E-mail: 13606120542@163.com

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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