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电针通过抑制脓毒症相关性脑病大鼠的HMGB1信号通路减轻神经炎症

Electroacupuncture Alleviates Neuroinflammation by Inhibiting the HMGB1 Signaling Pathway in Rats with Sepsis-Associated Encephalopathy.

作者信息

Xin Yueyang, Wang Jinxu, Chu Tiantian, Zhou Yaqun, Liu Cheng, Xu Aijun

机构信息

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.

Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.

出版信息

Brain Sci. 2022 Dec 17;12(12):1732. doi: 10.3390/brainsci12121732.

Abstract

Sepsis-Associated Encephalopathy (SAE) is common in sepsis patients, with high mortality rates. It is believed that neuroinflammation is an important mechanism involved in SAE. High mobility group box 1 protein (HMGB1), as a late pro-inflammatory factor, is significantly increased during sepsis in different brain regions, including the hippocampus. HMGB1 causes neuroinflammation and cognitive impairment through direct binding to advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4). Electroacupuncture (EA) at Baihui (GV20) and Zusanli (ST36) is beneficial for neurological diseases and experimental sepsis. Our study used EA to treat SAE induced by lipopolysaccharide (LPS) in male Sprague-Dawley rats. The Y maze test was performed to assess working memory. Immunofluorescence (IF) and Western blotting (WB) were used to determine neuroinflammation and the HMGB1 signaling pathway. Results showed that EA could improve working memory impairment in rats with SAE. EA alleviated neuroinflammation by downregulating the hippocampus's HMGB1/TLR4 and HMGB1/RAGE signaling, reducing the levels of pro-inflammatory factors, and relieving microglial and astrocyte activation. However, EA did not affect the tight junctions' expression of the blood-brain barrier (BBB) in the hippocampus.

摘要

脓毒症相关性脑病(SAE)在脓毒症患者中很常见,死亡率很高。人们认为神经炎症是SAE的一个重要机制。高迁移率族蛋白B1(HMGB1)作为一种晚期促炎因子,在脓毒症期间不同脑区(包括海马体)中显著升高。HMGB1通过直接与晚期糖基化终产物受体(RAGE)和Toll样受体4(TLR4)结合,导致神经炎症和认知障碍。针刺百会(GV20)和足三里(ST36)对神经系统疾病和实验性脓毒症有益。我们的研究使用针刺治疗雄性Sprague-Dawley大鼠中由脂多糖(LPS)诱导的SAE。进行Y迷宫试验以评估工作记忆。使用免疫荧光(IF)和蛋白质免疫印迹法(WB)来确定神经炎症和HMGB1信号通路。结果表明,针刺可以改善SAE大鼠的工作记忆障碍。针刺通过下调海马体中的HMGB1/TLR4和HMGB1/RAGE信号,降低促炎因子水平,减轻小胶质细胞和星形胶质细胞的激活,从而减轻神经炎症。然而,针刺并不影响海马体中血脑屏障(BBB)紧密连接的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d21/9776077/70f235ab024e/brainsci-12-01732-g001.jpg

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