体外炎症介质诱导星形胶质细胞反应性活化及功能差异比较分析

在中枢神经系统中，星形胶质细胞数量多、分布广，对神经元发挥正常功能起调节和支持作用。星形胶质细胞的胞体大且形态复杂多变，在正常生理状态下为静息态，在各类中枢神经系统疾病中存在着异常活化，活化导致其形态和功能发生变化，成为反应性星形胶质细胞。反应性星形胶质细胞的基因表达变化在不同疾病和组织区域之间具有显著差异。

许多炎症介质能诱导星形胶质细胞反应性活化，活化的星形胶质细胞炎症反应相关信号通路基因集的转录、表达水平发生变化。为了明确不同的神经炎症诱导介质诱导星形胶质细胞活化的特点及功能影响，本研究构建了3种炎症介质诱导的星形胶质细胞活化的体外实验模型，从转录水平层面上分析了不同诱导条件下的差异基因集，发现上调基因集的功能主要集中在抗病毒感染、细胞凋亡、NOD-like receptor等信号通路上。实验验证了各实验组Tnf 基因的上调、细胞凋亡发生、诱导型一氧化氮合酶表达变化。

本研究明确了LPS，TNF-α+IFN-γ，IL-1α+TNF-α+C1q，三种诱导炎症反应处理条件均能诱导星形胶质细胞发生以促炎因子表达上调为表型的反应性活化，诱导星形胶质细胞发生凋亡反应。

The central nervous system contains numerous and widely distributed astrocytes that regulate and support the normal functioning of neurons. Astrocytes have large cell bodies and diverse morphologies, and they remain in a resting state under normal physiological conditions. However, in various central nervous system diseases, astrocytes can undergo abnormal activation, leading to changes in their morphology and function, resulting in reactive astrocytes. The molecular expression changes of reactive astrocytes are highly variable between different diseases and regions of CNS.

Reactive activation of astrocytes can be induced by many inflammatory mediators, resulting in transcriptional and expression changes in the gene set associated with inflammatory responses. To clarify the characteristics and functional impacts of astrocyte activation induced by distinct inflammatory mediators, this study constructed three in vitro models of astrocyte activation. In this study, we established three in vitro experimental models of reactive astrocytes, with each model being induced by a specific combination of inflammatory mediators. Subsequently, we analyzed the differential expression of genes induced under these conditions. The up-regulated gene sets exhibited significant enrichment primarily in signaling pathways associated with antiviral infection, apoptosis, and NOD-like receptor activation. The present study confirmed the upregulation of Tnf genes, occurrence of apoptosis, and changes in the expression of inducible nitric oxide synthase in each experimental group.

This study demonstrated that LPS, TNF-α+IFN-γ, and IL-1α+TNF-α+C1q, all three treatments for inducing inflammatory responses, resulted in reactive activation of astrocytes. This was characterized by upregulation of pro-inflammatory factors, and an apoptotic response was induced in reactive astrocytes as well.

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