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温针灸疗法通过抑制 ERK 信号通路减轻脊髓损伤后的神经元凋亡。

Warm acupuncture therapy alleviates neuronal apoptosis after spinal cord injury via inhibition of the ERK signaling pathway.

机构信息

Department of Cardiovascular Medicine, Department of Hypertension, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Department of Acupuncture, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, People's Republic of China.

出版信息

J Spinal Cord Med. 2023 Sep;46(5):798-806. doi: 10.1080/10790268.2022.2088498. Epub 2022 Jul 6.

Abstract

PURPOSE

Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway.

METHODS

The rat SCI models were established by the impact method. SCI rat models were subjected to WA treatment at (GV14) and points (T10), (GV3), (ST36), and (BL32). The rat SCI models were established by the impact method. WA and U0126 treatments were performed on the SCI rats. Motor function and neuronal apoptosis were detected. The relative mRNA of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), the phosphorylation level of ERK 1/2 and levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and caspase-3 in spinal cord tissue were tested.

RESULTS

After WA treatment, the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale) of SCI rats in the WA treatment was significantly raised from 7 to 14 days after SCI. WA and U0126 treatment significantly diminished apoptotic cells and preserved the neurons in the injured spinal cord. WA and U0126 treatment alleviated the production of inflammatory cytokines in the spinal cord. The distinct increase of p-ERK 1/2 induced by SCI was reversed in WA and U0126 treatment groups. WA and U0126 treatment augmented the level of Bcl-2 and reversed the elevated cleaved caspase-3 protein level after SCI.

CONCLUSION

Our study demonstrated that WA might be associated with the downregulation of the ERK signaling pathway. In summary, our findings indicated that WA promotes the recovery of SCI via the protection of nerve cells and the prevention of apoptosis. Meanwhile, the anti-apoptotic effect of WA might be associated with the downregulation of the ERK signaling pathway, which could be one of the mechanisms of WA in the treatment of SCI.

摘要

目的

温针灸疗法已被应用于治疗脊髓损伤(SCI),但其潜在机制尚不清楚。本研究试图探讨温针灸疗法对 SCI 神经元凋亡的影响及其与细胞外信号调节激酶(ERK)信号通路的关系。

方法

采用打击法建立大鼠 SCI 模型。WA 治疗组大鼠在 T10 水平的 (GV14) 和 (GV3) 点、ST36 水平的 (ST36) 和 BL32 水平的 (BL32) 进行 WA 治疗。采用打击法建立 SCI 大鼠模型,对 SCI 大鼠进行 WA 和 U0126 治疗,检测运动功能和神经元凋亡情况,检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的相对 mRNA 水平,检测脊髓组织中 ERK1/2 的磷酸化水平和 B 细胞淋巴瘤-2(Bcl-2)、Bcl-2 相关 X(Bax)和半胱天冬酶-3 的水平。

结果

WA 治疗后,SCI 大鼠的 Basso、Beattie & Bresnahan 运动评分量表(BBB 量表)在 SCI 后 7 天至 14 天明显升高。WA 和 U0126 治疗显著减少了损伤脊髓中的凋亡细胞并保存了神经元。WA 和 U0126 治疗减轻了脊髓中炎症细胞因子的产生。WA 和 U0126 治疗组 SCI 诱导的 p-ERK1/2 明显增加被逆转。WA 和 U0126 治疗增加了 Bcl-2 的水平,并逆转了 SCI 后 cleaved caspase-3 蛋白水平的升高。

结论

本研究表明,WA 可能与 ERK 信号通路的下调有关。综上所述,我们的研究结果表明,WA 通过保护神经细胞和防止细胞凋亡来促进 SCI 的恢复。同时,WA 的抗凋亡作用可能与 ERK 信号通路的下调有关,这可能是 WA 治疗 SCI 的机制之一。

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