火针调节 Wnt/ERK 多条通路促进脊髓损伤大鼠神经干细胞向神经元分化。

Fire Needle Acupuncture Regulates Wnt/ERK Multiple Pathways to Promote Neural Stem Cells to Differentiate into Neurons in Rats with Spinal Cord Injury.

机构信息

The Second Hospital Affiliated to Tianjin University of Traditional Chinese Medicine, No. 69 Zengchan Road, Hebei District, Tianjin, China.

Tianjin Medical College, Tianjin, China.

出版信息

CNS Neurol Disord Drug Targets. 2019;18(3):245-255. doi: 10.2174/1871527318666190204111701.

BACKGROUND & OBJECTIVE: NSCs therapy is considered one of the most potential methods for spinal cord injury (SCI).

METHODS

We build the SCI model rats to investigate the therapeutic effect of fire needle acupuncture in improving the locomotor function of SCI rats and its possible mechanism. BBB scale was used for the motor ability of rats. The expression of Nestin, NSE, Gal-C, and GFAP was detected by immunohistochemistry. Wnt, GSK3β, β-catenin, ERK1/2, CyclinD1, and ngn1 were detected by western blot and PCR. The BBB score of both model group (1.20±0.94, 3.12±0.67, 5.34±1.57, 7.12±1.49) and fire needle group (1.70±0.58, 4.50±1.63, 7.53±2.41, 9.24±0.63) gradually increased after SCI. Furthermore, at d10 and d14, the fire needle group showed a significantly high score compared with that in model group at the same time (P<0.05). Fire needle increased Nestin, NSE, and Gal-C expression inhibited GFAP expression after SCI. Also, fire needle could up-regulate Wnt3a, GSK3β, β-catenin, and ngn1, and down-regulate ERK1/2, cyclinD1 gene and protein expression.

CONCLUSION

In conclusion, fire needle could improve lower limb locomotor function of SCI rats. Also, fire needles could promote endogenous NSCs proliferation differentiating into neurons, and the mechanism might be mediated by promoting the activation of Wnt/β-catenin and inhibiting the overexpression of ERK.

背景与目的

神经干细胞（NSCs）治疗被认为是脊髓损伤（SCI）最有潜力的方法之一。

方法

我们构建 SCI 大鼠模型，研究火针疗法改善 SCI 大鼠运动功能的治疗效果及其可能的机制。BBB 量表用于评估大鼠的运动能力。免疫组织化学法检测巢蛋白（Nestin）、神经特异性烯醇化酶（NSE）、半乳糖脑苷脂（Gal-C）和胶质纤维酸性蛋白（GFAP）的表达。Western blot 和 PCR 法检测 Wnt、GSK3β、β-catenin、ERK1/2、CyclinD1 和 ngn1 的表达。模型组（1.20±0.94、3.12±0.67、5.34±1.57、7.12±1.49）和火针组（1.70±0.58、4.50±1.63、7.53±2.41、9.24±0.63）的 BBB 评分在 SCI 后逐渐升高。此外，在 d10 和 d14 时，火针组在同一时间的评分明显高于模型组（P<0.05）。火针治疗可增加 SCI 后 NSCs 的增殖，促进其向神经元分化，并抑制星形胶质细胞的活化。火针还可以上调 Wnt3a、GSK3β、β-catenin 和 ngn1 的表达，下调 ERK1/2、cyclinD1 基因和蛋白的表达。