Electroacupuncture stimulation inhibited astrogliosis and microglia polarisation to alleviate spinal cord injury via Janus kinase 2/signal transducer and activator of transcription 3 signalling pathway.

IF 1.7 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jianuo Li, Yuhuai Guo, Xiangxin Zeng, Hongzhao Tian, Yapeng Han, Shuo Cai, Min Sun
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Abstract

Introduction: The aberrant activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway is involved in spinal cord injury (SCI) progression. Electroacupuncture (EA) stimulation is effective in alleviating SCI, but the mechanism is poorly understood.

Material and methods: An SCI model was constructed by cord contusion at T10, and AG490 (a JAK2 inhibitor) served as a positive control in this study. We evaluated the effects of EA on locomotor activity and spinal damage in SCI rats. The effects of EA on astrocytes and microglia and on the JAK2/STAT3 signalling pathway in the cells were investigated.

Results: Behavioural tests showed that hind limb motor function of rats was improved after EA stimulation. The therapeutic effects of EA stimulation in restoring motor function, alleviating injured spinal cords, and inhibiting spinal cord neuronal apoptosis in SCI rats, were similar to those of AG490. Increased STAT3 activation was observed in astrocytes and microglia in the spinal cord of SCI rats, and this was reversed by EA stimulation. EA alleviated astrogliosis and inhibited microglia M1 polarisation in SCI rat spinal cords. In addition, RNA expression levels of pro-inflammatory factors IL-6, CXCL1, and TNF-α in rat spinal cords were suppressed by EA stimulation, while the expression level of the anti-inflammatory factor heme oxygenase 1 was increased. Meanwhile, the expression of p-JAK2, p-STAT3, and JAK2/STAT3 downstream targets SOCS3 and COX-2 in the spinal cord of SCI rats was inhibited by EA stimulation. Interestingly, the observed effects were comparable to those treated with EA.

Conclusions: Our findings demonstrate that EA stimulation ameliorates SCI in rats and exerts an inhibitory effect on the JAK2/STAT3 signalling pathway.

电针刺激通过抑制星形胶质细胞形成和小胶质细胞极化,通过Janus激酶2/信号转导和转录3信号通路激活子减轻脊髓损伤。
JAK2/STAT3信号通路的异常激活参与脊髓损伤(SCI)的进展。电针(EA)刺激可有效缓解脊髓损伤,但其机制尚不清楚。材料和方法:在T10时建立脊髓损伤模型,以JAK2抑制剂AG490作为阳性对照。我们评估了EA对脊髓损伤大鼠运动活动和脊髓损伤的影响。研究了EA对星形胶质细胞和小胶质细胞以及细胞中JAK2/STAT3信号通路的影响。结果:行为学实验显示,EA刺激后大鼠后肢运动功能明显改善。EA刺激在恢复脊髓损伤大鼠运动功能、减轻脊髓损伤、抑制脊髓神经元凋亡等方面的治疗作用与AG490相似。在脊髓损伤大鼠的星形胶质细胞和小胶质细胞中观察到STAT3激活增加,这种情况被EA刺激逆转。EA减轻脊髓损伤大鼠星形胶质细胞增生,抑制小胶质细胞M1极化。此外,EA刺激可抑制大鼠脊髓中促炎因子IL-6、CXCL1和TNF-α的RNA表达水平,而抗炎因子血红素加氧酶1的表达水平升高。同时,EA刺激可抑制脊髓损伤大鼠p-JAK2、p-STAT3及JAK2/STAT3下游靶点SOCS3和COX-2的表达。有趣的是,观察到的效果与EA治疗的效果相当。结论:我们的研究结果表明,EA刺激可以改善大鼠的脊髓损伤,并对JAK2/STAT3信号通路产生抑制作用。
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来源期刊
Folia histochemica et cytobiologica
Folia histochemica et cytobiologica 生物-生化与分子生物学
CiteScore
2.80
自引率
6.70%
发文量
56
审稿时长
6-12 weeks
期刊介绍: "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.
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