AimsIntracerebral 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.MethodsICH 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.ResultsERBB1 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.ConclusionsERBB1 can improve SBI and has a neuroprotective effect in experimental ICH rats via PLC‐γ/PKC pathway.

中文翻译：

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ERBB1通过PLC-γ/PKC通路调节神经元死亡减轻大鼠实验性脑出血引起的继发性脑损伤

目的脑出血（ICH）是一种致残率和死亡率很高的疾病。本研究阐明表皮生长因子受体1(ERBB1)在脑出血中的作用。方法采用自体动脉血注入右侧基底节构建脑出血模型。通过蛋白质印迹分析检测ERBB1的蛋白水平。为了上调和下调大鼠中的 ERBB1，使用了 ERBB1 慢病毒过表达载体和 AG1478（ERBB1 的特异性抑制剂）进行脑室内注射。通过 TUNEL、尼氏染色和 ELISA 评估细胞凋亡、神经元损失和促炎细胞因子。同时，对ICH大鼠进行ERBB1靶向干预后的行为认知障碍进行评估。结果ICH大鼠脑组织中ERBB1显着升高。 ERBB1 的过度表达显着减少了 ICH 诱导的细胞凋亡和神经元损失，以及促炎细胞因子和氧化应激。同时，上调ERBB1后ICH大鼠的行为和认知障碍得到缓解；然而，AG1478治疗加重了继发性脑损伤（SBI）。此外，AG1478治疗逆转了ICH大鼠中PLC-γ和PKC的上调。结论ERBB1可以改善实验性ICH大鼠的SBI，并通过PLC-γ/PKC途径对实验性ICH大鼠具有神经保护作用。