中国临床药理学杂志

过表达NR2E1对糖尿病并发抑郁症大鼠海马齿状回神经再生的保护作用研究

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杜青 ¹ , 郭学俊 ¹ , 徐琳本 ¹ , 彭丽霞 ¹ , 柳卓 ²

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(9): 1275-1279

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (9) : 1275 -1279

过表达NR2E1对糖尿病并发抑郁症大鼠海马齿状回神经再生的保护作用研究

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杜青¹, 郭学俊¹, 徐琳本¹, 彭丽霞¹, 柳卓²

作者信息

^1.湖南省中医药研究院医学实验动物中心，湖南长沙 410013

^2.湖南省中西医结合医院科研科，湖南长沙 410006

通讯作者:

柳卓，副研究员 MP: 13469438403 E-mail: 330811844@qq.com

作者简介:

杜青（1991-），女，硕士，助理研究员，主要从事中药神经/精神药理的相关研究

Research on the protective effects of overexpression of NR2E1 on nerve regeneration in dentate gyrus of hippocampus in diabetic rats complicated with depression

Qing DU¹, Xue-jun GUO¹, Lin-ben XU¹, Li-xia PENG¹, Zhuo LIU²

Affiliations

^1.Medical Experimental Animal Center, Hunan Institute of Traditional Chinese Medicine, Changsha 410013, Hunan Province, China

^2.Scientific Research Section, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, Changsha 410006, Hunan Province, China

出版时间: 2025-05-17 doi: 10.13699/j.cnki.1001-6821.2025.09.013

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摘要

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目的

探讨孤儿核受体TLX（NR2E1）过表达对糖尿病并发抑郁症大鼠海马齿状回（DG）神经再生的保护作用。

方法

用尾静脉注射链脲佐菌素联合慢性不可预测性温和刺激复制糖尿病并发抑郁症大鼠模型。将造模成功的大鼠随机分为模型组、对照组和实验组，每组8只；另取8只正常大鼠设为正常组。对照组注射腺相关对照病毒4 μL；实验组注射NR2E1过表达腺相关病毒4 μL；模型组和正常组均注射等量0.9% NaCl。给药结束14 d后，用Morris水迷宫检测大鼠抑郁样行为，用血糖仪检测空腹血糖水平，用酶联免疫吸附试验法检测血清胰岛素（INS）和海马DG区白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平，用免疫荧光法检测海马DG区胸苷类似物溴脱氧尿苷（Brdu）蛋白的表达情况，用实时荧光定量聚合酶链反应法检测微小RNA-let-7d（miRNA-let-7d）/NR2E1/沉默信息调节因子1（SIRT1）基因的表达水平。

结果

实验组、对照组、模型组和正常组的空间探索时间分别为（31.25±9.94）、（25.50±8.02）、（19.75±5.82）和（43.87±12.77）s，空腹血糖分别为（19.28±3.60）、（25.26±5.25）、（23.71±4.13）和（4.45±0.40）mmoL·L^-1，胰岛素水平分别为（77.15±3.03）、（80.53±4.93）、（83.31±5.77）和（48.15±5.18）ng·mL^-1，IL-1β水平分别为（28.15±4.68）、（36.83±6.97）、（40.18±4.40）和（19.15±2.67）pg·mL^-1，TNF-α水平分别为（281.15±25.15）、（324.06±16.85）、（337.08±23.11）和（219.06±27.68）pg·mL^-1，Brdu积分光密度值分别为1.70±1.19、0.89±0.12、0.93±0.14和2.14±0.15，miRNA-let-7d相对表达水平分别为2.02±0.18、2.67±0.54、2.88±0.30和1.11±0.16，NR2E1 mRNA相对表达水平分别为2.87±0.39、0.96±0.09、1.07±0.12和3.29±0.35，SIRT1 mRNA相对表达水平分别为1.62±0.37、0.99±0.08、1.04±0.10和2.30±0.34。实验组的上述指标与模型组比较，在统计学上差异均有统计学意义（均P<0.05）。

结论

NR2E1过表达可能通过调控miRNA-let-7d/NR2E1/SIRT1信号传导，从而保护糖尿病并发抑郁症大鼠海马DG神经再生。

关键词

孤儿核受体TLX / 微小RNA-let-7d / 沉默信息调节因子1 / 糖尿病并发抑郁症 / 海马齿状回

Abstract

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Objective

To explore the protective effects of orphan nuclear receptor subfamily 2 group E member 1 (NR2E1) overexpression on nerve regeneration in dentate gyrus (DG) of diabetic rats complicated with depression.

Methods

The rat model of diabetes complicated with depression was established by injecting streptozotocin into the tail vein combined with chronic unpredictable mild stimulation. The successful rats were randomly divided into model, control and experimental groups, with 8 rats per group; another 8 normal rats were set as normal group. Control group was injected adeno-associated control virus 4 μL. Experimental group was injected with adeno-associated virus of overexpress NR2E1 4 μL; model and normal groups were injected with 0.9% NaCl. After 14 days, the depression-like behavior of rats was detected by Morris water maze, the fasting blood glucose level was detected by blood glucose meter, and the serum insulin (INS), interleukin -1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in DG area were detected by enzyme-linked immunosorbent assay. The expression of thymidine analogue bromodeoxyuridine (Brdu) in DG region was detected by immunofluorescence method, and the signal transduction expression levels of microRNA-let-7d (miRNA-let-7d)/NR2E1/silencing information regulatory factor 1 (SIRT1) gene were detected by real-time fluorescence quantitative polymerase chain reaction.

Results

The space exploration time of experimental, control, model and normal groups was (31.25±9.94), (25.50±8.02), (19.75±5.82) and (43.87±12.77) s; the fasting blood glucose were (19.28±3.60), (25.26±5.25), (23.71±4.13) and (4.45±0.40) mmoL·L^-1; the insulin levels were (77.15±3.03), (80.53±4.93), (83.31±5.77) and (48.15±5.18) ng·mL^-1; the IL-1β levels were (28.15±4.68), (36.83±6.97), (40.18±4.40) and (19.15±2.67) pg·mL^-1; the TNF-α levels were (281.15±25.15), (324.06±16.85), (337.08±23.11) and (219.06±27.68) pg·mL^-1; the integrated optical density of Brdu were 1.70±1.19, 0.89±0.12, 0.93±0.14 and 2.14±0.15; the relative expression levels of miRNA-let-7d were 2.02±0.18, 2.67±0.54, 2.88±0.30 and 1.11±0.16; the relative expression levels of NR2E1 mRNA were 2.87±0.39, 0.96±0.09, 1.07±0.12 and 3.29±0.35; the relative expression levels of SIRT1 mRNA were 1.62±0.37, 0.99±0.08, 1.04±0.10 and 2.30±0.34, respectively. Compared with the model group, the above indexes in experimental group have statistical significance (all P<0.05).

Conclusion

The overexpression of NR2E1 receptor in isolated nucleus may protect the dentate gyrus nerve regeneration in diabetic rats with depression by regulating miRNA-let-7d/TLX/SIRT1 signal transduction.

Key words

orphan nuclear receptor subfamily 2 group E member 1 / microRNA-let-7d / silent information regulator 1 / diabetes complicated with depression / dentate gyrus of hippocampus

引用本文

杜青, 郭学俊, 徐琳本, 彭丽霞, 柳卓. 过表达NR2E1对糖尿病并发抑郁症大鼠海马齿状回神经再生的保护作用研究. 中国临床药理学杂志, 2025 , 41 (9) : 1275 -1279 . DOI: 10.13699/j.cnki.1001-6821.2025.09.013

Qing DU, Xue-jun GUO, Lin-ben XU, Li-xia PENG, Zhuo LIU. Research on the protective effects of overexpression of NR2E1 on nerve regeneration in dentate gyrus of hippocampus in diabetic rats complicated with depression[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (9) : 1275 -1279 . DOI: 10.13699/j.cnki.1001-6821.2025.09.013

基金

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国家自然科学基金资助项目(82305203; 82104839)
湖南省自然科学基金资助项目(2023JJ60456; 2023JJ40402)
长沙市自然科学基金资助项目(kq2208142)
湖南省中医药研究院一般课题资助项目(202106)
长沙市杰出创新青年资助项目(KQ2306028)

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2025年第41卷第9期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.09.013

接收时间：2024-12-01
首发时间：2026-08-04
出版时间：2025-05-17

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收稿日期：2024-12-01

基金

国家自然科学基金资助项目(82305203; 82104839)

湖南省自然科学基金资助项目(2023JJ60456; 2023JJ40402)

长沙市自然科学基金资助项目(kq2208142)

湖南省中医药研究院一般课题资助项目(202106)

长沙市杰出创新青年资助项目(KQ2306028)

作者信息

^1.湖南省中医药研究院医学实验动物中心，湖南长沙 410013

^2.湖南省中西医结合医院科研科，湖南长沙 410006

通讯作者:

柳卓，副研究员 MP: 13469438403 E-mail: 330811844@qq.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.09.013

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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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