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ERBB1 通过调节 PLC-γ/PKC 通路减轻大鼠实验性脑出血引起的继发性脑损伤。

ERBB1 alleviates secondary brain injury induced by experimental intracerebral hemorrhage in rats by modulating neuronal death via PLC-γ/PKC pathway.

机构信息

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

Department of Neurosurgery, Yancheng City No. 1 People's Hospital, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, Jiangsu Province, China.

出版信息

CNS Neurosci Ther. 2024 Mar;30(3):e14679. doi: 10.1111/cns.14679.

DOI:10.1111/cns.14679
PMID:38528842
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10964039/
Abstract

AIMS

Intracerebral hemorrhage (ICH) is a disease with high rates of disability and mortality. The role of epidermal growth factor receptor 1 (ERBB1) in ICH was elucidated in this study.

METHODS

ICH model was constructed by injecting autologous arterial blood into the right basal ganglia. The protein level of ERBB1 was detected by western blot analysis. To up- and downregulation of ERBB1 in rats, intraventricular injection of a lentivirus overexpression vector of ERBB1 and AG1478 (a specific inhibitor of ERBB1) was used. The cell apoptosis, neuronal loss, and pro-inflammatory cytokines were assessed by TUNEL, Nissl staining, and ELISA. Meanwhile, behavioral cognitive impairment of ICH rats was evaluated after ERBB1-targeted interventions.

RESULTS

ERBB1 increased significantly in brain tissue of ICH rats. Overexpression of ERBB1 remarkably reduced cell apoptosis and neuronal loss induced by ICH, as well as pro-inflammatory cytokines and oxidative stress. Meanwhile, the behavioral and cognitive impairment of ICH rats were alleviated after upregulation of ERBB1; however, the secondary brain injury (SBI) was aggravated by AG1478 treatment. Furthermore, the upregulation of PLC-γ and PKC in ICH rats was reversed by AG1478 treatment.

CONCLUSIONS

ERBB1 can improve SBI and has a neuroprotective effect in experimental ICH rats via PLC-γ/PKC pathway.

摘要

目的

脑出血（ICH）是一种致残率和死亡率都很高的疾病。本研究旨在阐明表皮生长因子受体 1（ERBB1）在 ICH 中的作用。

方法

通过向右侧基底节注射自体动脉血构建 ICH 模型。采用 Western blot 分析检测 ERBB1 的蛋白水平。通过脑室注射 ERBB1 的慢病毒过表达载体和 AG1478（ERBB1 的特异性抑制剂）来上调和下调大鼠 ERBB1。通过 TUNEL、尼氏染色和 ELISA 评估细胞凋亡、神经元丢失和促炎细胞因子。同时，在 ERBB1 靶向干预后评估 ICH 大鼠的行为认知障碍。

结果

ICH 大鼠脑组织中 ERBB1 明显增加。过表达 ERBB1 可显著减少 ICH 引起的细胞凋亡和神经元丢失，以及促炎细胞因子和氧化应激。同时，上调 ERBB1 可减轻 ICH 大鼠的行为和认知障碍；然而，AG1478 治疗加重了继发性脑损伤（SBI）。此外，AG1478 处理可逆转 ICH 大鼠中 PLC-γ 和 PKC 的上调。

结论

ERBB1 可通过 PLC-γ/PKC 通路改善实验性 ICH 大鼠的 SBI 并具有神经保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/8508ee28b5d3/CNS-30-e14679-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/f6b804fc6f05/CNS-30-e14679-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/2f92ba0f05df/CNS-30-e14679-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/af8fee4d1320/CNS-30-e14679-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/3d5b9c43c67b/CNS-30-e14679-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/18a69b45f4ff/CNS-30-e14679-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/8508ee28b5d3/CNS-30-e14679-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/f6b804fc6f05/CNS-30-e14679-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/2f92ba0f05df/CNS-30-e14679-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/af8fee4d1320/CNS-30-e14679-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/3d5b9c43c67b/CNS-30-e14679-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/18a69b45f4ff/CNS-30-e14679-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9a5/10964039/8508ee28b5d3/CNS-30-e14679-g002.jpg

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