首都医科大学学报 ›› 2021, Vol. 42 ›› Issue (2): 251-256.doi: 10.3969/j.issn.1006-7795.2021.02.015

• 基础研究 • 上一篇    下一篇

蛋白激酶Pbk在缺氧神经胶质细胞中的变化及与IGF-1的相关性

王雨晴1,2, 陈志刚1, 李芳芳2, 张斯佳2, 罗玉敏2, 赵海苹2,*   

  1. 1. 北京中医药大学东方医院脑病科, 北京 100029;
    2.首都医科大学宣武医院脑血管病研究室, 北京 100053
  • 收稿日期:2020-07-21 发布日期:2021-04-26
  • 基金资助:
    国家自然科学基金(81771412,81971222);

Changes of Pbk and its correlation with cytokine IGF-1 in glial cells after oxygen and glucose deprivation

Wang Yuqing1, 2, Chen Zhigang1, Li Fangfang2, Zhang Sijia2, Luo Yumin2, Zhao Haiping2, *   

  1. 1.Department of Encephalopathy, Dongfang Hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China;
    2.Cerebrovascular Diseases Research Institute, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
  • Received:2020-07-21 Published:2021-04-26
  • Contact: *E-mail:zhaohaipin91980@163.com
  • Supported by:
    This study was supported by National Natural Science Foundation of China (81771412,81971222).

摘要: 目的 探讨神经胶质细胞缺氧缺糖后不同时间点蛋白激酶Pbk的变化及与胰岛素样生长因子-1(insulin-like growth factors-1,IGF-1)的相关性。方法 培养BV2小胶质细胞、分离原代星形胶质细胞,制备氧糖剥夺(oxygen and glucose deprivation,OGD)模型,采用反转录聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)技术观察信号分子Pbk、组蛋白去乙酰化酶2(histone deacetylases 2, HDAC2)以及IGF-1在两种胶质细胞OGD处理1、3、6 h后的表达情况,并对信号分子和细胞因子进行了Pearson相关性分析。结果 随着OGD时间延长,Pbk的转录水平在小胶质细胞中先升后降,在星形胶质细胞中逐渐升高,组间差异有统计学意义(P<0.05)。HDAC2的转录水平在小胶质细胞中逐渐下降,在星形胶质细胞中逐渐升高,组间差异有统计学意义(P<0.05)。IGF-1的转录水平在小胶质细胞中逐渐下降,在星形胶质细胞中逐渐升高,组间差异有统计学意义(P<0.05)。细胞缺氧缺糖后信号分子Pbk以及HDAC2在小胶质细胞和星形胶质细胞中的转录水平与IGF-1的转录水平均呈正相关关系(P<0.05)。结论 缺血缺氧性损伤早期营养因子IGF-1在小胶质细胞中的分泌减少,在星形胶质细胞中的分泌增加,可能与Pbk/HDAC2/IGF-1这一通路激活相关。

关键词: 缺血缺氧, 小胶质细胞, 星形胶质细胞, 细胞因子, PDZ连接激酶

Abstract: Objective To investigate the changes of PDZ-binding-kinase(Pbk) and its correlation with cytokine insulin-like growth factors-1(IGF-1) in glial cells at different time points after oxygen and glucose deprivation.Methods BV2 microglia cells were cultured, primary astrocytes were isolated, and the oxygen and glucose deprivation(OGD) model was prepared. The expressions of cytokines IGF-1 and signal molecules Pbk and HDAC2 in two kinds of glia cells after 1, 3 and 6 h of oxygen and glucose deprivation were observed by reverse transcription-polymerase chain reaction(RT-PCR). Pearson correlation analysis of cytokines and signal molecules was carried out. Results With the time extension of OGD, the transcription level of Pbk was increased firstly and then decreased in microglia cells, and gradually increased in astrocytes, with statistically significant differences between groups (P<0.05). The transcription level of HDAC2 was decreased gradually in microglia cells and increased gradually in astrocytes, with statistically significant differences between groups (P<0.05). The transcription level of IGF-1 was decreased gradually in microglia cells and increased gradually in astrocytes, with statistically significant differences between groups (P<0.05).The transcription levels of Pbk and HDAC2 in microglia cells and astrocytes were positively correlated with the transcription level of IGF-1 after oxygen and glucose deprivation (P<0.05).Conclusion During the early stage of hypoxic-ischemic injury, the secretion of IGF-1 decreased in microglia and increased in astrocyte, which may be related to the activation of the Pbk/HDAC2/IGF-1 pathway. It provides a basis for further research on the neuroprotective mechanism after ischemia.

Key words: ischemia and hypoxia, microglia, astrocyte, cytokines, PDZ binding kinase

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