中国临床药理学杂志

罗哌卡因抑制小鼠脑中的cGAS/STING通路减轻脓毒症相关脑病的研究

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林熙宇 ¹ , 高婕 ² , 巩凯悦 ² , 陆俐 ² , 彭义畅 ³ , 晁亚丽 ⁴ , 宋成洁 ⁵

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(17): 2459-2464

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (17) : 2459 -2464

罗哌卡因抑制小鼠脑中的cGAS/STING通路减轻脓毒症相关脑病的研究

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林熙宇¹, 高婕², 巩凯悦², 陆俐², 彭义畅³, 晁亚丽⁴, 宋成洁⁵

作者信息

^1.徐州医科大学第二临床医学院，江苏徐州 221004

^2.徐州医科大学第一临床医学院，江苏徐州 221004

^3.徐州医科大学麻醉学院，江苏徐州 221004

^4.徐州医科大学附属医院重症监护室，江苏徐州 221003

^5.徐州医科大学基础医学院生理学教研室，徐州市生理功能与损伤重点实验室，江苏徐州 221004

通讯作者:

宋成洁，副教授 MP: 13913478280 E-mail: songcj09@xzhmu.edu.cn

作者简介:

林熙宇（2003-），男，本科生，主要从事儿科学方向的相关研究

Research on the inhibition of the cGAS/STING pathway in the brain by ropivacaine alleviates sepsis-related encephalopathy in mice

Xi-yu LIN¹, Jie GAO², Kai-yue GONG², Li LU², Yi-chang PENG³, Ya-li ZHAO⁴, Cheng-jie SONG⁵

Affiliations

^1.The Second Clinical School of Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China

^2.The First Clinical School of Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China

^3.School of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China

^4.Department of Intensive Care Unit, Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221003, Jiangsu Province, China

^5.Department of physiology, School of Basic Medical Sciences, Xuzhou Key Laboratory of Physiological Function and Injury, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China

出版时间: 2025-09-17 doi: 10.13699/j.cnki.1001-6821.2025.17.011

文章导航

摘要

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目的

探究罗哌卡因对脓毒性脑病（SAE）模型小鼠脑胶质细胞环磷酸鸟苷-磷酸腺苷合酶-干扰素基因刺激因子（cGAS/STING）通路的影响，及其相关作用机制。

方法

将小鼠随机分为空白组、模型组、实验组和对照组，每组15只。除空白组和对照组外，其余2组用脂多糖腹腔注射法建立脓毒症小鼠模型。实验组和对照组均腹腔注射0.3 mg·kg^-1·d^-1罗哌卡因；空白组和模型组均腹腔注射等体积0.9%NaCl。4组小鼠每天给药1次，连续给药7 d。用Morris水迷宫检测小鼠脑认知功能，用实时荧光定量聚合酶链反应法检测小鼠脑炎症因子mRNA水平，用蛋白质印迹法检测小鼠脑cGAS和STING蛋白相对表达水平，用免疫荧光染色法检测cGAS/STING通路相关蛋白的荧光强度相对值。

结果

空白组、模型组、实验组和对照组的探索时间占比分别为（0.48±0.10）%、（0.23±0.05）%、（0.37±0.04）%和（0.46±0.07）%，平台穿越次数分别为（4.67±0.48）、（1.03±0.11）、（2.50±0.65）和（4.99±0.52）次，逃避潜伏时间分别为（11.92±0.98）、（12.49±1.22）、（11.17±1.43）和（12.21±1.52）min，白细胞介素（IL）-1β mRNA相对表达水平分别为1.00±0.10、3.80±0.28、1.87±0.13和1.06±0.29，IL-18 mRNA相对表达水平分别为1.00±0.12、1.61±0.27、1.06±0.08和0.97±0.05，肿瘤坏死因子（TNF）-α mRNA相对表达水平分别为1.00±0.13、2.02±0.18、1.05±0.09和1.13±0.11，IL-6 mRNA相对表达水平分别为1.00±0.08、1.56±0.11、1.05±0.09和0.93±0.06，cGAS蛋白相对表达水平分别为1.00±0.08、1.92±0.19、1.42±0.11和1.03±0.10，STING蛋白相对表达水平分别为1.00±0.12、2.01±0.22、1.18±0.09和1.08±0.16，cGAS蛋白荧光强度相对值分别为1.00±0.18、1.88±0.15、1.57±0.09和1.03±0.11，STING荧光强度相对值分别为1.00±0.16、1.79±0.26、1.14±0.06和1.20±0.29，胱天蛋白酶3（caspase-3）蛋白荧光强度相对值分别为1.00±0.12、1.51±0.08、1.23±0.10和1.11±0.15。实验组和对照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

罗哌卡因通过抑制cGAS/STING通路可以减轻SAE小鼠脑海马区胶质细胞凋亡，对SAE小鼠的脑部具有保护作用。

关键词

罗哌卡因 / 脓毒性脑病 / 脑胶质细胞 / 环磷酸鸟苷-磷酸腺苷合酶-干扰素基因刺激因子信号通路

Abstract

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Objective

To explore the effects of ropivacaine on the cyclic guanosine monophosphate synthase interferon gene stimulating factor (cGAS/STING) pathway in glial cells of septic encephalopathy (SAE) model mice, and its related mechanisms of action.

Methods

Mice were randomly divided into blank group, model group, experimental group and control group, with 15 mice in each group. Except for the blank group and control group, the other two groups were used to establish sepsis mouse models by intraperitoneal injection of lipopolysaccharide. The experimental group and control group were intraperitoneally injected with 0.3 mg·kg^-1·d^-1 ropivacaine, while the blank group and model group were intraperitoneally injected with an equal volume of 0.9% NaCl. The four groups of mice were administered once a day for 7 consecutive days. The Morris water maze was used to detect the cognitive function of the mouse brain, real-time fluorescent quantitative polymerase chain reaction was used to detect the mRNA levels of brain inflammatory factors, Western blot was used to detect the expression levels of brain cGAS and STING proteins, and immunofluorescence staining was used to detect the expression of apoptosis-related proteins.

Results

The exploration time proportions of the blank group, model group, experimental group and control group were (0.48±0.10)%, (0.23±0.05)%, (0.37±0.04)% and (0.46±0.07)%, respectively; the platform crossing times were (4.67±0.48), (1.03±0.11), (2.50±0.65) and (4.99±0.52) times, respectively; the escape latency time was (11.92±0.98), (12.49±1.22), (11.17±1.43) and (12.21±1.52) min, respectively; the relative expression levels of interleukin-1β (IL-1β) mRNA were 1.00±0.10, 3.80±0.28, 1.87±0.13 and 1.06±0.29, respectively; the relative expression levels of IL-18 mRNA were 1.00±0.12, 1.61±0.27, 1.06±0.08 and 0.97±0.05, respectively; the relative expression levels of tumor necrosis factor (TNF)-α mRNA were 1.00±0.13, 2.02±0.18, 1.05±0.09 and 1.13±0.11, respectively; the relative expression levels of IL-6 mRNA were 1.00±0.08, 1.56±0.11, 1.05±0.09 and 0.93±0.06, respectively; the relative expression levels of cGAS protein were 1.00±0.08, 1.92±0.19, 1.42±0.11 and 1.03±0.10, respectively; the relative expression levels of STING protein were 1.00±0.12, 2.01±0.22, 1.18±0.09 and 1.08±0.16, respectively; the relative fluorescence intensities of cGAS protein were 1.00±0.18, 1.88±0.15, 1.57±0.09 and 1.03±0.11, respectively; the relative fluorescence intensities of STING were 1.00±0.16, 1.79±0.26, 1.14±0.06 and 1.20±0.29, respectively; the relative fluorescence intensities of caspase-3 protein were 1.00±0.12, 1.51±0.08, 1.23±0.10, and 1.11±0.15, respectively. The above indexes of the experimental group and the control group were statistically different from the model group (all P<0.05).

Conclusion

Ropivacaine can alleviate apoptosis of glial cells in the hippocampus of SAE mice by inhibiting the cGAS/STING pathway, and has a protective effect on the brain of SAE mice.

Key words

ropivacaine / septic encephalopathy / brain glial cell / cyclic guanosine monophosphate synthase interferon gene stimulating factor signaling pathway

引用本文

林熙宇, 高婕, 巩凯悦, 陆俐, 彭义畅, 晁亚丽, 宋成洁. 罗哌卡因抑制小鼠脑中的cGAS/STING通路减轻脓毒症相关脑病的研究. 中国临床药理学杂志, 2025 , 41 (17) : 2459 -2464 . DOI: 10.13699/j.cnki.1001-6821.2025.17.011

Xi-yu LIN, Jie GAO, Kai-yue GONG, Li LU, Yi-chang PENG, Ya-li ZHAO, Cheng-jie SONG. Research on the inhibition of the cGAS/STING pathway in the brain by ropivacaine alleviates sepsis-related encephalopathy in mice[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (17) : 2459 -2464 . DOI: 10.13699/j.cnki.1001-6821.2025.17.011

基金

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江苏省自然科学基金资助项目(BK20231182)
博士后科学基金资助项目(RC5052003)
徐州市卫生委员会医学研究基金资助项目(XWKYHT20230074)

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2025年第41卷第17期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.17.011

接收时间：2024-11-20
首发时间：2026-08-05
出版时间：2025-09-17

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收稿日期：2024-11-20

基金

江苏省自然科学基金资助项目(BK20231182)

博士后科学基金资助项目(RC5052003)

徐州市卫生委员会医学研究基金资助项目(XWKYHT20230074)

作者信息

^1.徐州医科大学第二临床医学院，江苏徐州 221004

^2.徐州医科大学第一临床医学院，江苏徐州 221004

^3.徐州医科大学麻醉学院，江苏徐州 221004

^4.徐州医科大学附属医院重症监护室，江苏徐州 221003

^5.徐州医科大学基础医学院生理学教研室，徐州市生理功能与损伤重点实验室，江苏徐州 221004

通讯作者:

宋成洁，副教授 MP: 13913478280 E-mail: songcj09@xzhmu.edu.cn

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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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