中国临床药理学杂志

瑞马唑仑改善术后认知功能障碍小鼠学习记忆能力和脑损伤的研究

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汪云飞 ^1a , 王加芳 ^1a , 丁喆 ^1b , 张朋 ^1a , 姚万军 ^1a , 冯艳坤 ^1a

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(7): 955-961

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (7) : 955 -961

瑞马唑仑改善术后认知功能障碍小鼠学习记忆能力和脑损伤的研究

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汪云飞^1a, 王加芳^1a, 丁喆^1b, 张朋^1a, 姚万军^1a, 冯艳坤^1a

作者信息

^1a.武汉市第一医院，麻醉科，湖北武汉 430033

^1b.武汉市第一医院，疼痛科，湖北武汉 430033

通讯作者:

王加芳，副主任医师，硕士生导师 MP: 13995660701 E-mail: doctorwjf66@163.com

作者简介:

汪云飞（1985-），男，主治医师，主要从事麻醉药物镇痛机制研究、急危重症患者的麻醉与救治、麻醉与认知功能方面的相关研究

Research of remimazolam improving learning and memory ability and brain injury in postoperative cognitive dysfunction mice

Yun-fei WANG^1a, Jia-fang WANG^1a, Zhe DING^1b, Peng ZHANG^1a, Wan-jun YAO^1a, Yan-kun FENG^1a

Affiliations

^1a.Department of Anesthesiology, Wuhan First Hospital, Wuhan 430033, Hubei Province, China

^1b.Department of Pain, Wuhan First Hospital, Wuhan 430033, Hubei Province, China

出版时间: 2025-04-17 doi: 10.13699/j.cnki.1001-6821.2025.07.011

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摘要

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目的

探讨瑞马唑仑通过调控NOD样受体热蛋白结构域相关蛋白3（NLRP3）改善术后认知功能障碍（POCD）小鼠学习记忆能力和脑损伤的相关机制。

方法

将C57BL/6J小鼠分为假手术组（仅暴露胫骨，不进行截断）、模型组（截断胫骨术方法构建POCD模型）、对照组（建模+15 mg·kg^-1瑞马唑仑处理+尾静脉注射60 nmol·L^-1oe-NC）、过表达组（建模+15 mg·kg^-1瑞马唑仑处理+尾静脉注射60 nmol·L^-1oe-NLRP3）和低、中、高剂量组（建模后分别给予5、10、15 mg·kg^-1瑞马唑仑腹腔注射），每组12只。处理后的小鼠，用Morris水迷宫和跳台实验评估学习和记忆能力，用实时荧光定量聚合酶链反应检测NLRP3、白细胞介素1β（IL-1β）、IL-10、肿瘤坏死因子-α（TNF-α）的表达水平，用2′，7′-二氯二氢荧光素二乙酸酯（DCFH-DA）染色法检测活性氧（ROS）水平，用免疫荧光法检测胶质纤维酸性蛋白（GFAP）水平。

结果

假手术组、模型组和低、中、高剂量组的穿越平台次数分别为（4.58±0.91）、（0.73±0.15）、（0.92±0.18）、（1.58±0.31）和（2.75±0.55）次，错误次数分别为（0.50±0.11）、（2.08±0.41）、（1.75±0.35）、（1.58±0.31）和（1.25±0.25）次，NLRP3 mRNA相对表达水平分别为1.00±0.15、3.51±0.69、2.94±0.59、2.57±0.51和1.91±0.38；假手术组、模型组、高剂量组、对照组、过表达组的IL-1β mRNA相对表达水平分别为1.00±0.17、2.72±0.54、1.87±0.37、1.91±0.38和2.66±0.53，IL-10 mRNA相对表达水平分别为1.00±0.16、0.51±0.10、0.78±0.15、0.73±0.15和0.56±0.11，TNF-α mRNA相对表达水平分别为1.00±0.21、3.08±0.61、1.77±0.35、1.82±0.36和2.65±0.53，ROS相对荧光强度分别为1.00±0.16、7.22±1.45、3.05±0.61、3.13±0.63和6.75±1.31，GFAP相对荧光强度分别为1.00±0.18、6.71±1.13、3.38±0.63、3.50±0.72和5.94±1.19。假手术组的上述指标与模型组比较，高剂量组的上述指标与模型组比较，过表达组的上述指标与对照组比较，在统计学上差异均有统计学意义（均P<0.05）。

结论

瑞马唑仑可以改善小鼠的术后认知功能，其机制可能与下调NLRP3表达来抑制神经炎症和氧化应激损伤有关。

关键词

瑞马唑仑 / NOD样受体热蛋白结构域相关蛋白3 / 术后认知功能障碍 / 活性氧 / 炎症反应 / 神经元

Abstract

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Objective

To explore the mechanism of remimazolam improving learning and memory ability and brain injury in postoperative cognitive impairment (POCD) mice by regulating NOD-like receptor heat protein domain associated protein 3 (NLRP3).

Methods

The C57BL/6J mice were divided into sham group (exposure of the tibia only without truncation), model group (tibia ampution method to construct POCD model), oe-NC group (modeling+15 mg·kg^-1 remimazolam treatment+tail vein injection of 60 nmol·L^-1oe-NC), oe-NLRP3 group (modeling+15 mg·kg^-1 remimazolam treatment+tail vein injection of 60 nmol·L^-1oe-NLRP3), experimental-L, -M, -H groups (after modeling, 5, 10, 15 mg·kg^-1 remimazolam was respectively given intraperitoneal injection), 12 rats per group. For the treated mice, the Morris water maze and step - down test were used to evaluate their learning and memory abilities. The expression levels of NLRP3, interleukin-1β (IL-1β), IL-10 and tumor necrosis factor-α (TNF-α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The level of reactive oxygen species (ROS) was detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and the level of glial fibrillary acidic protein (GFAP) was detected by immunofluorescence.

Results

The platform crossing times of sham operation group, model group and experimental-L, -M, -H groups were (4.58±0.91), (0.73±0.15), (0.92±0.18), (1.58±0.31) and (2.75±0.55), respectively; the error times were (0.50±0.11), (2.08±0.41), (1.75±0.35), (1.58±0.31) and (1.25±0.25), respectively; the relative expression levels of NLRP3 mRNA were 1.00±0.15, 3.51±0.69, 2.94±0.59, 2.57±0.51 and 1.91±0.38, respectively; the relative expression levels of IL-1β mRNA in sham operation group, model group, experimental-H group, control group and oe-NLRP3 group were 1.00±0.17, 2.72±0.54, 1.87±0.37, 1.91±0.38 and 2.66±0.53, respectively; the relative expression levels of IL-10 mRNA were 1.00±0.16, 0.51±0.10, 0.78±0.15, 0.73±0.15 and 0.56±0.11, respectively; the relative expression levels of TNF-α mRNA were 1.00±0.21, 3.08±0.61, 1.77±0.35, 1.82±0.36 and 2.65±0.53, respectively; the relative fluorescence intensities of ROS were 1.00±0.16, 7.22±1.45, 3.05±0.61, 3.13±0.63 and 6.75±1.31, respectively; the relative fluorescence intensities of GFAP were 1.00±0.18, 6.71±1.13, 3.38±0.63, 3.50±0.72 and 5.94±1.19, respectively. The above indexes in the sham operation group were compared with the model group, the above indexes in the experimental-H group were compared with the model group, the above indexes in the oe-NLRP3 group were compared with the control group, and the differences were statistically significant (all P<0.05).

Conclusion

Remimazolam improves postoperative cognitive function in mice by a mechanism that may be related to the inhibition of neuroinflammatory and oxidative stress damage by down-regulating NLRP3 expression.

Key words

remimazolam / NOD-like receptor heat protein domain associated protein 3 / postoperative cognitive dysfunction / reactive oxygen species / inflammatory response / neurons

引用本文

汪云飞, 王加芳, 丁喆, 张朋, 姚万军, 冯艳坤. 瑞马唑仑改善术后认知功能障碍小鼠学习记忆能力和脑损伤的研究. 中国临床药理学杂志, 2025 , 41 (7) : 955 -961 . DOI: 10.13699/j.cnki.1001-6821.2025.07.011

Yun-fei WANG, Jia-fang WANG, Zhe DING, Peng ZHANG, Wan-jun YAO, Yan-kun FENG. Research of remimazolam improving learning and memory ability and brain injury in postoperative cognitive dysfunction mice[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (7) : 955 -961 . DOI: 10.13699/j.cnki.1001-6821.2025.07.011

基金

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武汉市医学科学研究基金资助项目(WX23B15)

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2025年第41卷第7期

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doi: 10.13699/j.cnki.1001-6821.2025.07.011

接收时间：2024-10-29
首发时间：2026-08-04
出版时间：2025-04-17

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收稿日期：2024-10-29

基金

武汉市医学科学研究基金资助项目(WX23B15)

作者信息

^1a.武汉市第一医院，麻醉科，湖北武汉 430033

^1b.武汉市第一医院，疼痛科，湖北武汉 430033

通讯作者:

王加芳，副主任医师，硕士生导师 MP: 13995660701 E-mail: doctorwjf66@163.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.07.011

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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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