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新白杨素通过调节 CREB1 预防异氟醚麻醉诱导的新生小鼠认知功能障碍。

Neobaicalein prevents isoflurane anesthesia-induced cognitive impairment in neonatal mice via regulating CREB1.

机构信息

Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Clinics (Sao Paulo). 2023 Apr 28;78:100201. doi: 10.1016/j.clinsp.2023.100201. eCollection 2023.

DOI:10.1016/j.clinsp.2023.100201
PMID:37120983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10173397/
Abstract

OBJECTIVES

Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage.

METHOD

The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels.

RESULTS

Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under iso-treatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1-positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein.

CONCLUSIONS

Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.

摘要

目的

异氟醚(ISO)在临床和研究中被广泛应用。作者旨在探讨新白杨素(Neob)是否能保护新生小鼠免受 ISO 诱导的认知损伤。

方法

采用旷场试验、水迷宫试验和悬尾试验评估小鼠的认知功能。酶联免疫吸附试验用于评估炎症相关蛋白浓度。免疫组织化学用于评估离子钙结合衔接分子-1(IBA-1)表达。采用细胞计数试剂盒-8 检测海马神经元活力。双免疫荧光染色用于确认蛋白质之间的相互作用。Western blot 用于评估蛋白表达水平。

结果

Neob 显著改善了认知功能,表现出抗炎作用;此外,在 ISO 处理下,它表现出神经保护作用。此外,Neob 抑制了 ISO 处理小鼠中白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6 水平的升高,并上调了白细胞介素-10 水平。Neob 显著减轻了 ISO 诱导的新生小鼠海马中 IBA-1 阳性细胞数量的增加。此外,它抑制了 ISO 诱导的神经元凋亡。机制上,Neob 被观察到通过上调 cAMP 反应元件结合蛋白(CREB1)磷酸化来保护海马神经元免受 ISO 介导的凋亡。此外,它挽救了 ISO 诱导的突触蛋白异常。

结论

Neob 通过抑制凋亡和炎症来预防 ISO 麻醉引起的认知障碍,从而上调 CREB1。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/98e7f9500c1a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/eda33c956059/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/059469f29b2e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/766516dd039a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/b898c5c739fd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/98e7f9500c1a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/eda33c956059/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/059469f29b2e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/766516dd039a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/b898c5c739fd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de1a/10173397/98e7f9500c1a/gr5.jpg

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