Electroacupuncture improves locomotor function by regulating expression of inflammation and oxidative stress-related proteins in mice with spinal cord injury. - GreenMedInfo Summary

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of apolipoprotein E (ApoE) and related proteins of inflammation and anti-oxidative stress in spinal cord in mice with spinal cord injury (SCI), so as to explore its mechanisms underlying function repair.

METHODS: Thirty-six female C57BL/6 mice were equally randomized into 3 groups: sham operation, model and EA. The SCI model was established by clamping the spinal cord for 25 s with a serrefine after laminectomy of the 1lumbar vertebra (L1). EA (1.5 Hz/7.5 Hz, 1.0 mA) was applied to bila-teral"Zusanli"(ST36) and"Sanyinjiao"(SP6) for 10 min, once a day for 7 days. The hindlimb locomotor function was assessed according to the state of the range of motion, coordination, claw gesture of the hind leg ankle-joint, trunk stabi-lity and the tail posture by using Basso Mouse Scale(BMS). The histopathological changes of the injured area of the spinal cord were determined by H.E. staining. The expression levels of ApoE, phosphorylated nuclear transcription factor-κB(p-NF-κB), interleukin 1 beta(IL-1β), phosphorylated extracellular regulatory protein kinase(p-ERK1/2), extracellular regulatory protein kinase(ERK1/2), nuclear factor erythroid 2-related factor 2(Nrf2) and heme oxidase-1(HO-1) in the spinal cord were detected by Western blot, and the glial fibrillary acidic protein (GFAP)-positive astrocytes were displayed by immunofluorescence staining.

RESULTS: After modeling, the BMS scores were significantly decreased in the model group compared with the sham operation group (<0.05). Following EA, the BMS scores were markedly increased in the EA group relevant to the model group (<0.05), suggesting an improvement of the hindlimb locomotor function. H.E. stain showed structural disorder with lots of cavities, severe inflammatory infiltration with large quantity of inflammatory cells, and apparent reduction of normal neurons in the injured spinal cord tissue of model group, which was milder in the EA group. The expression levels of ApoE, p-NF-κB, IL-1β, p-ERK1/2 (not ERK1/2), Nrf2 and HO-1 were significantly increased in the model group than those in the sham operation group (<0.05). Compared with the model group, the expression levels of ApoE, p-ERK1/2, Nrf2 and HO-1 were further notably up-regulated (<0.05), and those of p-NF-κB and IL-1β proteins obviously down-regulated in the EA group (<0.05). Immunoflorescence staining showed that the number of GFAP-positive cells was apparently increased in the model group compared with the sham operation group and observably decreased in the EA group relevant to the model group (<0.05).

CONCLUSION: EA can significantly improve locomotor function in SCI mice, which is associated with its effects in reducing inflammation, oxi-dative stress reactions and reactive astrocyte proliferation via up-regulating expression of ApoE, p-ERK1/2, and Nrf2/HO-1 (antioxidant pathway) and inhibiting IL-1β and NF-κB expression.