利多卡因对脓毒症相关性脑病细胞模型的影响及机制  

The Effect and Mechanism of Lidocaine on a Sepsis-Associated Encephalopathy Cell Model

作　　者：张宇轩 刘一丹 马琳 李瑞轩 闫强 徐桂萍[3] ZHANG Yuxuan;LIU Yidan;MA Lin;LI Ruixuan;YAN Qiang;XU Guiping(Graduate School of Xinjiang Medical University,Urumqi Xinjiang 830000,China;Department of Anesthesiology,Affiliated Tumor Hospital of Xinjiang Medical University,Urumqi Xinjiang 830000,China;Department of Anesthesiology,People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi Xinjiang 830000,China)

机构地区：[1]新疆医科大学研究生学院,新疆乌鲁木齐830000 [2]新疆医科大学附属肿瘤医院麻醉科,新疆乌鲁木齐830000 [3]新疆维吾尔自治区人民医院麻醉科,新疆乌鲁木齐830000

出　　处：《临床研究》2025年第5期5-9,共5页Clinical Research

基　　金：自治区研究生创新项目(XJ2023G203)。

摘　　要：目的探讨利多卡因对脓毒症相关性脑病细胞模型的影响及相关机制。方法选取出生3天之内的SD大鼠的乳鼠,从乳鼠大脑皮质中分离出星形胶质细胞,随后使用不同的培养基进行培养。其中,仅以DMEM高糖培养基培养的为空白对照组(Sham组),用加入脂多糖(LPS)的DMEM高糖培养基培养的为脓毒症相关性脑病组(SAE组),用同时加入脂多糖及利多卡因(LD)的DMEM高糖培养基培养的为脓毒症相关性脑病利多卡因干预组(SAE+LD组),培养时间均为48 h。ELISA法检测细胞培养的上清液白介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平,Western-Blot法检测高迁移率族蛋白B_(1)(HMGB_(1))、核转录因子-κB(NF-κB)、Toll样受体4(TLR4)的表达水平,免疫荧光检测HMGB_(1)、TLR4、NF-κB表达情况,流式细胞术检测细胞凋亡情况。结果和Sham组相比,SAE组、SAE+LD组细胞培养上清液中IL-6、TNF-α浓度显著增高,差异有统计学意义(P<0.05);和SAE组相比,SAE+LD组细胞培养上清液中IL-6、TNF-α浓度显著降低,差异有统计学意义(P<0.05)。与Sham组相比,SAE组、SAE+LD组细胞中HMGB_(1)、TLR4、NF-κB表达显著增高,差异有统计学意义(P<0.05);和SAE组相比,SAE+LD组细胞中HMGB_(1)、TLR4、NF-κB表达显著降低,差异有统计学意义(P<0.05)。结论利多卡因可能通过抑制HMGB_(1)蛋白而产生抗炎作用,具体机制可能与抑制星形胶质细胞中的HMGB_(1)转位的有关。Objective To investigate the effects of lidocaine on a sepsis-associated encephalopathy cell model and the underlying mechanisms.Methods Neonatal SD rats within three days of birth were selected to isolate astrocytes from the cerebral cortex.The cells were then cultured using different culture media.The control group(Sham group)was cultured using high-glucose DMEM alone,while the sepsis-associated encephalopathy group(SAE group)was cultured with high-glucose DMEM supplemented with lipopolysaccharide(LPS).The sepsis-associated encephalopathy lidocaine intervention group(SAE+LD group)was cultured with high-glucose DMEM containing both LPS and lidocaine(LD).The culture duration was 48 hours.The levels of interleukin 6(IL-6)and tumor necrosis factorα(TNF-α)in the cell culture supernatant were measured using the ELISA method.The expression levels of high mobility group box 1(HMGB_(1)),nuclear factor-κB(NF-κB),and Toll-like receptor 4(TLR4)were detected using Western Blot analysis,while HMGB_(1),TLR4,and NF-κB expression were assessed using immunofluorescence.Flow cytometry was used to detect cell apoptosis.Results Compared to the Sham group,the concentrations of IL-6 and TNF-α in the culture supernatants of the SAE and SAE+LD groups were significantly increased,with a statistically significant difference(P<0.05).Compared to the SAE group,the concentrations of IL-6 and TNF-α in the SAE+LD group were significantly decreased,with a statistically significant difference(P<0.05).Compared to the Sham group,the expression levels of HMGB_(1),TLR4,and NF-κB in the SAE and SAE+LD groups were significantly increased,with a statistically significant difference(P<0.05).Compared to the SAE group,the expression levels of HMGB_(1),TLR4,and NF-κB in the SAE+LD group were significantly decreased,with a statistically significant difference(P<0.05).Conclusion Lidocaine may exert anti-inflammatory effects by inhibiting HMGB_(1)protein,and the specific mechanism may be related to the suppression of HMGB_(1)translocation in astrocyt

关 键 词：脓毒症相关性脑病 利多卡因 星形胶质细胞 炎症介质 信号通路 

分 类 号：R742.7[医药卫生—神经病学与精神病学]