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胰岛素样生长因子结合蛋白 6 与大鼠脑出血后神经元凋亡的关系。

Insulin-like Growth Factor Binding Protein6 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage in Rats.

机构信息

Department of Orthopedics, Traditional Chinese Medicine Hospital of Haian County Affiliated Hospital, Nanjing University of Chinese Medicine of Hanlin College, Ninghai Road, Haian County, 226600, Jiangsu Province, China.

Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu Province, China.

出版信息

Cell Mol Neurobiol. 2017 Oct;37(7):1207-1216. doi: 10.1007/s10571-016-0453-1. Epub 2017 Jan 2.

Abstract

The insulin-like growth factor (IGF) system is linked to CNS pathological states. The functions of IGFs are modulated by a family of binding proteins termed insulin-like growth factor binding proteins (IGFBPs). Here, we demonstrate that IGFBP-6 may be associated with neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). We obtained a significant upregulation of IGFBP-6 in neurons adjacent to the hematoma following ICH with the results of Western blot, immunohistochemistry, and immunofluorescence. Increasing IGFBP-6 level was found to be accompanied by the upregulation of Bax, Bcl-2, and active caspase-3. Besides, IGFBP-6 co-localized well with active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. Knocking down IGFBP-6 by RNA-interference in PC12 cells reduced active caspase-3 expression. Thus, IGFBP-6 may play a role in promoting the brain secondary damage following ICH.

摘要

胰岛素样生长因子(IGF)系统与中枢神经系统病理状态有关。IGFs 的功能受胰岛素样生长因子结合蛋白(IGFBPs)家族的调节。在这里,我们证明 IGFBP-6 可能与脑出血(ICH)过程中的神经元凋亡有关。我们通过 Western blot、免疫组织化学和免疫荧光法发现,ICH 后血肿周围神经元中 IGFBP-6 显著上调。研究发现,IGFBP-6 水平的升高伴随着 Bax、Bcl-2 和活性 caspase-3 的上调。此外,IGFBP-6 在神经元中与活性 caspase-3 共定位,表明其在神经元凋亡中可能发挥作用。在 PC12 细胞中通过 RNA 干扰敲低 IGFBP-6 可降低活性 caspase-3 的表达。因此,IGFBP-6 可能在促进脑出血后的脑继发性损伤中发挥作用。

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