针灸通过介导 ERK1/2/Cx43 轴调节星形胶质细胞神经毒性极化，保护延迟溶栓中血脑屏障的完整性

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-04-11 DOI:10.1016/j.ibneur.2025.04.005

Zhi-Hui Zhang , Yu Gu , Zheng Huang , Xin-Yu Liu , Wen-Tao Xu , Xin-Chang Zhang , Guang-Xia Ni

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引用次数: 0

摘要

背景：溶栓治疗仍然是急性缺血性卒中的标准治疗方法。溶栓的狭窄窗口意味着治疗的延迟会加重脑损伤。星形胶质细胞调节血脑屏障（BBB）的完整性和神经炎症，但它们的神经毒性极化加剧了神经病理条件下的损伤，包括缺血性中风。延迟重组组织纤溶酶原激活物（rt-PA）溶栓破坏星形胶质细胞稳态，进一步加重脑损伤。本研究探讨针刺作为一种重要的中医疗法，是否通过调节星形胶质细胞神经毒性极化来减轻迟发性溶栓所致的损伤，并阐明其潜在的信号通路。方法建立延迟rt-PA溶栓大鼠栓塞性脑卒中模型。评估针刺对梗死面积、血脑屏障完整性和神经炎症的影响。进行大量和单细胞转录组分析以评估星形胶质细胞特异性转录变化。Western blotting、免疫荧光和药理学抑制实验验证了分子机制。结果针刺减少梗死面积，改善神经功能，恢复血脑屏障完整性。转录组学分析揭示针刺干预后星形胶质细胞神经毒性极化的动态调节。进一步的验证实验表明，针刺抑制ERK1/2-Cx43级联，从而减弱星形胶质细胞介导的神经毒性。该通路的药理调节复制了针刺的保护作用，强调了减轻星形胶质细胞功能障碍和促进血脑屏障恢复的作用。结论针刺可通过ERK1/2-Cx43通路调节星形胶质细胞极化，减轻迟发性溶栓所致脑损伤。这些发现强调了针灸作为一种潜在的策略来提高缺血性卒中溶栓治疗的安全性。

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Acupuncture regulates astrocyte neurotoxic polarization to protect blood–brain barrier integrity in delayed thrombolysis through mediating ERK1/2/Cx43 axis

Background

Thrombolytic therapy remains the standard treatment for acute ischemic stroke. The narrow window for thrombolysis means that delay in treatment worsens brain injury. Astrocytes regulate blood-brain barrier (BBB) integrity and neuroinflammation, yet their neurotoxic polarization exacerbates injury in neuropathological conditions, including ischemic stroke. Delayed recombinant tissue plasminogen activator (rt-PA) thrombolysis disrupts astrocyte homeostasis, further aggravating brain injury. This study investigates whether acupuncture, a key therapy in traditional Chinese medicine, alleviates delayed thrombolysis-induced injury by modulating astrocyte neurotoxic polarization and elucidates the underlying signaling pathway.

Methods

A rat model of embolic stroke with delayed rt-PA thrombolysis was established. The effects of infarct volume, BBB integrity, and neuroinflammation of acupuncture were evaluated. Bulk and single-cell transcriptomic analyses were performed to assess astrocyte-specific transcriptional changes. Western blotting, immunofluorescence, and pharmacological inhibition experiments validated molecular mechanisms.

Results

Acupuncture reduced infarct volume, improved neurological function, and restored BBB integrity. Transcriptomic analysis revealed dynamic regulation of astrocyte neurotoxic polarization following acupuncture intervention. Further validation experiments demonstrated that acupuncture suppressed the ERK1/2-Cx43 cascade, thereby attenuating astrocyte-mediated neurotoxicity. Pharmacological modulation of this pathway replicated the protective effects of acupuncture, highlighting the role in mitigating astrocyte dysfunction and promoting BBB recovery.

Conclusion

Acupuncture mitigates delayed thrombolysis-induced brain injury by modulating astrocyte polarization via the ERK1/2-Cx43 pathway. These findings highlight acupuncture as a potential strategy to enhance thrombolytic therapy safety in ischemic stroke.

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