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电针通过TNF-α介导的ERK1/2/P2XR信号通路减轻SD大鼠干眼性眼痛

Electroacupuncture Alleviates Dry Eye Ocular Pain Through TNF-ɑ Mediated ERK1/2/P2XR Signaling Pathway in SD Rats.

作者信息

Wan Mi-Mi, Jin Tuo, Fu Zhang-Yitian, Lai Si-Hua, Gao Wei-Ping

机构信息

Department of Ophthalmology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.

Department of Ophthalmology, Kunshan Hospital of Chinese Medicine, Suzhou, People's Republic of China.

出版信息

J Pain Res. 2023 Dec 12;16:4241-4252. doi: 10.2147/JPR.S436258. eCollection 2023.

Abstract

PURPOSE

This study aimed to examine electroacupuncture's influence on ocular pain and its potential modulation of the TNF-ɑ mediated ERK1/2/P2XR signaling pathway in dry eye-induced rat models.

METHODS

Male Sprague-Dawley rats with induced dry eye, achieved through extraorbital lacrimal gland removal, were treated with electroacupuncture. Comprehensive metrics such as the corneal mechanical perception threshold, palpebral fissure height, eyeblink frequency, eye wiping duration, behavioral changes in the open field test, and the forced swimming test were employed. Additionally, morphological changes in microglia and neurons were observed. Expression patterns of key markers, TNF-ɑ, TNFR1, p-ERK1/2, and P2XR, in the trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (SpVc) regions, were studied with etanercept serving as a control to decipher the biochemistry of electroacupuncture's therapeutic effects.

RESULTS

Electroacupuncture treatment demonstrated a notable decrease in the corneal mechanical perception threshold, improvement in palpebral fissure height, and significant reductions in both eyeblink frequency and eye wiping duration. Moreover, it exhibited a promising role in anxiety alleviation. Notably, the technique effectively diminished ocular pain by curbing microglial and neuronal activation in the TG and SpVc regions. Furthermore, it potently downregulated TNF-ɑ, TNFR1, p-ERK1/2, and P2XR expression within these regions.

CONCLUSION

Electroacupuncture attenuated damage to sensory nerve pathways, reduced pain, and eased anxiety in dry eye-afflicted rats. The findings suggest a crucial role of TNF-ɑ mediated ERK1/2/P2XR signaling pathway inhibition by electroacupuncture in these benefits.

摘要

目的

本研究旨在探讨电针疗法对眼痛的影响及其对干眼诱导大鼠模型中肿瘤坏死因子-α(TNF-α)介导的细胞外信号调节激酶1/2(ERK1/2)/嘌呤能受体P2X7(P2XR)信号通路的潜在调节作用。

方法

通过摘除眶外泪腺诱导雄性Sprague-Dawley大鼠患干眼,然后对其进行电针治疗。采用了综合指标,如角膜机械感觉阈值、睑裂高度、眨眼频率、擦眼持续时间、旷场试验和强迫游泳试验中的行为变化。此外,还观察了小胶质细胞和神经元的形态变化。以依那西普作为对照,研究三叉神经节(TG)和三叉神经尾侧脊髓核(SpVc)区域中关键标志物TNF-α、肿瘤坏死因子受体1(TNFR1)、磷酸化ERK1/2(p-ERK1/2)和P2XR的表达模式,以解读电针治疗效果的生物化学机制。

结果

电针治疗使角膜机械感觉阈值显著降低,睑裂高度得到改善,眨眼频率和擦眼持续时间均显著减少。此外,它在缓解焦虑方面也表现出良好的作用。值得注意的是,该技术通过抑制TG和SpVc区域的小胶质细胞和神经元激活,有效减轻了眼痛。此外,它还强烈下调了这些区域内TNF-α、TNFR1、p-ERK1/2和P2XR的表达。

结论

电针减轻了干眼大鼠感觉神经通路的损伤,减轻了疼痛,并缓解了焦虑。研究结果表明,电针抑制TNF-α介导的ERK1/2/P2XR信号通路在这些益处中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fa1/10725190/40b342cc6410/JPR-16-4241-g0001.jpg

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