Study of the pathology and the underlying molecular mechanism of tissue injury around hematoma following intracerebral hemorrhage

Study of the pathology and the underlying molecular mechanism of tissue injury around hematoma following intracerebral hemorrhage
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脑出血后血肿周围组织损伤的病理及分子机制研究

DOI:
10.3892/mmr.2021.12341
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发表时间:
2021-08
影响因子:
3.4
通讯作者:
Kaifu Ke
Kaifu Ke
中科院分区:
医学4区
文献类型:
--
作者:
Jinglei Wang;Ying Chen;Jingjing Liang;Maosheng Cao;Jiabing Shen;Kaifu Ke

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脑出血(ICH)是指脑部血管自发性破裂引起的出血。 ICH 引起的脑损伤会因血肿形成和溶解红细胞成分引起的氧化应激而导致灾难性后果。然而,并非血肿周围区域的所有神经元都会立即死亡:许多神经元仍处于临界但可逆的状态;然而,我们对参与这种临界状态的基因仍然知之甚少。使用基因芯片技术识别血肿周围区域与 210 个基因上调和 173 个基因下调相关的变化。基因本体功能注释揭示了脑出血后血肿周围区域基因表达谱的变化,这些变化主要与机体受到外界刺激,通过细胞膜蛋白的转运向细胞传递有害信息,以及一系列生物过程的调节有关。蛋白质相互作用网络分析显示,11个上行分泌磷蛋白1、双特异性磷酸酶9、儿茶酚-O-甲基转移酶、含BAR/IMD结构域的接头蛋白2-like 1、plakophilin 2、homer支架蛋白3、ret原癌基因(RET)、KIT原癌基因、受体酪氨酸激酶、hepsin、Ras激酶抑制子的连接器增强子2和kalirin RhoGEF 激酶]和四个下调基因(转录因子 AP-2β、肽基脯氨酰异构酶 A、SHOC2 富含亮氨酸重复支架蛋白和突触核蛋白 α)可能在 ICH 后血肿周围区域发挥重要作用。采用逆转录定量PCR验证这些基因在ICH中与对照组相比存在差异表达。因果网络分析表明,Achaete-scute 同源物 1-RET 信号轴在 ICH 后血肿周围区域神经损伤的修复中发挥关键作用。此外,体内实验表明 RET 表达上调并与神经元共定位。综上所述,这些结果表明,ICH后血肿周围区域基因表达谱的变化主要与神经系统损伤的修复有关。
Intracerebral hemorrhage (ICH) refers to hemorrhage caused by spontaneous rupture of blood vessels in the brain. Brain injury due to ICH leads to catastrophic effects resulting from the formation of hematoma and oxidative stress caused by components of lysed erythrocytes. However, not all neurons in the area surrounding the hematoma die immediately: A number of neurons remain in a critical, but reversible, state; however, the genes involved in this critical state remain poorly understood. Gene chip technology was used identify changes in the area surrounding the hematoma associated with the upregulation of 210 and downregulation of 173 genes. Gene Ontology functional annotation revealed changes in the gene expression profile in the peripheral region of hematoma following ICH, which were primarily associated with the external stimulation received by the organism, the transmission of harmful information to the cell through the transport of cell membrane proteins, and the regulation of a series of biological processes. Protein interaction network analysis revealed that 11 up-[secreted phosphoprotein 1, dual specificity phosphatase 9, catechol-O-methyltransferase, BAR/IMD domain-containing adaptor protein 2-like 1, plakophilin 2, homer scaffold protein 3, ret proto-oncogene (RET), KIT proto-oncogene, receptor tyrosine kinase, hepsin, connector enhancer of kinase suppressor of Ras 2 and kalirin RhoGEF kinase] and four downregulated genes (transcription factor AP-2β, peptidylprolyl isomerase A, SHOC2 leucine rich repeat scaffold protein and synuclein α) may serve a significant role in the area around hematoma following ICH. Reverse transcription-quantitative PCR was used to verify that these genes were differentially expressed in the ICH compared with the control group. Causal network analysis suggested that the Achaete-scute homolog 1-RET signaling axis served a key role in the repair of nerve injury in the peripheral region of hematoma following ICH. Additionally, in vivo experiments revealed that RET expression was upregulated and co-localized with neurons. Taken together, these results suggested that the changes in the gene expression profile in the area around hematoma following ICH were primarily associated with the repair of damage caused to the nervous system.
干细胞疗法:一种有前景的脑出血治疗方法
DOI: 10.1177/0963689718773363
发表时间: 2018-12
影响因子: 3.3
作者:
Gao L;Xu W;Li T;Chen J;Shao A;Yan F;Chen G
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通过(18)F-FDG-PET成像和葡萄糖转运蛋白表达在脑出血的小鼠模型中分析葡萄糖代谢。
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通讯作者: Koehler RC
DOI: --
发表时间: 2015-04
期刊: Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology
影响因子: --
作者:
Zhiqing Zeng;Hong Liu;D. Jiang
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DOI: 10.1186/s12967-021-02903-5
发表时间: 2021-05-28
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作者:
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DOI: 10.1186/s12974-017-0790-0
发表时间: 2017-02-14
影响因子: 9.3
作者:
Wu J;Sun L;Li H;Shen H;Zhai W;Yu Z;Chen G
通讯作者: Chen G