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Electro-Acupuncture treatment Promotes Regeneration and Recovery of Spinal Cord Injured Nerve by Regulating HIF-1α/VEGF Signal Pathway

Abstract

Weibing-Wei, Lingyao-Zhou, Hongsheng-Zhang, Zhengxin-Li, Yu-Yang and Binbin-Zhou*

Objective: The present study aimed to explore the effect of Electro-acupuncture (EA) on the mechanism of nerve regeneration and recovery in spinal cord injury rats by interfering with the expressions of factors associated with HIF-1α/VEGF signaling pathway, covering HIF-1α, VEGF, PKA, Synapsin I, CaMKII as well as BDNF.

Methods: 120 SD female rats after achieving the successful modeling of spinal cord injury were randomly split into Jia ji EA group (EA-1 group), Yang ming EA group (EA-2 group), as well as Sham group(n=48 per groups); subsequently, the rats were split into 5 subgroups (1-5week group, n=8 per subgroups). EA treatment was performed on the 3rd day after the mice achieved the modeling, and specimens were taken at different time points after the treatment. BBB score was employed to assess the variations of lower limb function in mice after they had spinal cord injury. Histological variations of mice after they had spinal cord injury were observed under an optical microscope after undergoing HE staining. The variation of positive cell count was characterized under an optical microscope. RT-PCR and WB techniques were adopted to identify the variations of mRNA and protein expressions of factors associated with HIF-1α/VEGF signaling pathway.

Results: Over time, the lower limb function of mice having spinal cord injury was to a certain extent recovered, and EA-1 and EA-2 groups were more obviously recovered than the control group. According to the results of HE staining, as compared with Sham group, the nerve cell structure of EA-1 and EA-2 groups could be noticeably repaired, and the number of neurons was remarkably up-regulated. As suggested by immunohistochemical results, the number of positive cells in the injured site of Sham group was evidently risen in EA-1 and EA-2 groups as compared with that of Sham Group. PCR and WB results indicated that EA-treatment could up-regulate the expressions of HIF-1α, VEGF, PKA, Synapsin I, BDNF genes, as well as the corresponding proteins, while suppressing the expressions of CaMKII genes and their corresponding proteins. The expression of EA-2 group was partially better than that of EA-1 group.

Conclusion: EA treatment can stimulate the expression of HIF-1α, VEGF, PKA, synapsin I, CaMKII, BDNF mRNA and their corresponding proteins associated with the activation pathway of HIF-1α/VEGF signal transduction pathway. Moreover, this treatment is capable of regulating blood oxygen microenvironment (e.g., local energy consumption, oxygen consumption and blood circulation) after rats get injured, while being critical to the recovery of spinal cord injury.