同源结构域相互作用蛋白激酶2修饰的大鼠脊髓星形胶质细胞对脊髓损伤后神经功能恢复的影响

IF 2 4区医学 Q3 CLINICAL NEUROLOGY Current neurovascular research Pub Date : 2022-01-01 DOI:10.2174/1567202619666220601111715

Renbo Li, Jian Han, Bo Chen, Jingbo Shang

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引用次数: 0

摘要

背景:脊髓损伤(SCI)被认为是一种急性神经系统疾病，星形胶质细胞在脊髓损伤的进展中起着重要作用。目的:研究HIPK2修饰的大鼠脊髓星形胶质细胞在脊髓损伤后神经功能恢复中的作用。方法:培养、分离大鼠脊髓星形胶质细胞，通过显微镜观察和免疫荧光染色进行鉴定。用过表达HIPK2的腺病毒载体感染星形胶质细胞进行修饰，用细胞计数试剂盒-8法和流式细胞术检测星形胶质细胞的增殖和凋亡情况。用星形胶质细胞或hipk2修饰的星形胶质细胞治疗SCI大鼠模型。随后，采用BBB评分法和斜平面法分析大鼠运动能力，苏木精-伊红染色和尼索染色观察脊髓组织损伤和神经元存活情况。检测HIPK2、脑源性神经营养因子(BDNF)、胶质细胞系源性神经营养因子(GDNF)、白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α、核因子红系2相关转录因子2 (Nrf2)/抗氧化反应元件(ARE)通路相关蛋白的水平。结果:成功收获大鼠脊髓星形胶质细胞。HIPK2过表达可促进大鼠脊髓星形胶质细胞增殖，抑制细胞凋亡。大鼠脊髓星形胶质细胞处理增加了脊髓损伤大鼠血脑屏障点和最大稳定角度，改善了脊髓组织损伤，增加了神经元数量，减轻了神经损伤和炎症，而hipk2修饰的大鼠脊髓星形胶质细胞处理对脊髓损伤大鼠神经功能恢复的作用更为明显。同时，hipk2修饰的大鼠脊髓星形胶质细胞进一步激活Nrf2/ARE通路。结论:hipk2修饰的大鼠脊髓星形胶质细胞促进脊髓损伤后神经功能恢复，激活Nrf2/ARE通路。

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Homeodomain Interacting Protein Kinase 2-Modified Rat Spinal Astrocytes Affect Neurofunctional Recovery After Spinal Cord Injury.

Background: Spinal cord injury (SCI) is regarded as an acute neurological disorder, and astrocytes play a role in the progression of SCI.

Objective: Herein, we investigated the roles of homeodomain-interacting protein kinase 2 (HIPK2)- modified rat spinal astrocytes in neurofunctional recovery after SCI.

Methods: Rat spinal astrocytes were cultured, isolated, and then identified through microscopic observation and immunofluorescence staining. Astrocytes were infected with the adenovirus vector overexpressing HIPK2 for modification, and proliferation and apoptosis of astrocytes were examined using Cell Counting Kit-8 method and flow cytometry. SCI rat models were established and treated with astrocytes or HIPK2-modified astrocytes. Subsequently, rat motor ability was analyzed via the Basso-Beattie-Bresnahan (BBB) scoring and inclined-plane test, and the damage to spinal cord tissues and neuronal survival were observed via Hematoxylin-eosin staining and Nissl staining. The levels of HIPK2, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and nuclear factor erythroid 2- related transcription factor 2 (Nrf2)/antioxidant response element (ARE) pathway-related proteins were detected.

Results: Rat spinal astrocytes were harvested successfully. HIPK2 overexpression accelerated the proliferation and repressed the apoptosis of rat spinal astrocytes. Rat spinal astrocytes treatment increased BBB points and the maximum angle at which SCI rats remained stable, ameliorated damage to spinal cord tissues, increased the number of neurons, and attenuated neural damage and inflammation, while the treatment of HIPK2-modified rat spinal astrocytes imparted more pronounced effects to the neurofunctional recovery of SCI rats. Meanwhile, HIPK2-modified rat spinal astrocytes further activated the Nrf2/ARE pathway.

Conclusion: HIPK2-modified rat spinal astrocytes facilitated neurofunctional recovery and activated the Nrf2/ARE pathway after SCI.

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来源期刊

Current neurovascular research 医学-临床神经学

CiteScore

3.80

自引率

9.50%

发文量

审稿时长

3 months

期刊介绍： Current Neurovascular Research provides a cross platform for the publication of scientifically rigorous research that addresses disease mechanisms of both neuronal and vascular origins in neuroscience. The journal serves as an international forum publishing novel and original work as well as timely neuroscience research articles, full-length/mini reviews in the disciplines of cell developmental disorders, plasticity, and degeneration that bridges the gap between basic science research and clinical discovery. Current Neurovascular Research emphasizes the elucidation of disease mechanisms, both cellular and molecular, which can impact the development of unique therapeutic strategies for neuronal and vascular disorders.