[Anti-inflammation mechanism of electro-scalp acupuncture in treatment of ischemic stroke based on IL-12 mediated JAK/STAT signaling pathway].

OBJECTIVE

To observe the impact of electro-scalp acupuncture (ESA) on the neural function and inflammatory response of ischemic cortex in the model rats with ischemic stroke and explore the anti-inflammation mechanism of ESA in treatment of ischemic stroke from the perspective of modulating the interleukin 12 (IL-12) mediated JAK (Janus kinase)/STAT (signal transduction and transcription activator) signal pathway.

METHODS

Ninety male SD rats were randomized into a normal group ( =16) and a model preparation group (=74). In the model preparation group, the model of middle cerebral artery occlusion (MCAO) was duplicated with suture-occlusion method. After modeled successfully, 48 rats with neurological deficit score of 1-3 were divided into a model group, an inhibitor group and an ESA group, 16 rats in each one. In the inhibitor group, IL-12 inhibitor (apilimod, 5 mg/kg) was used via intragastric administration. In the ESA group, the anterior oblique line of vertex-temporal (MS6) was stimulated bilaterally with electric acupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in current intensity. The needles were retained for 30 min. The treatment was given once daily and for 7 days in above two intervention groups. Before and after intervention, the neurological deficit score (NDS) and neurobehavioral score (NBS) were assessed in each group. HE staining method was adopted to observe the morphological manifestations of ischemic cortical lesion; the concentrations of IL-12 and IL-12R of the brain tissue in the ischemic cortical lesion were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of STAT4 and Tbx21 were detected by real-time PCR technique; and the protein expression of IL-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-4 were detected using immunohistochemistry.

RESULTS

NDS and NBS in the model group, the inhibitor group and the ESA group were all higher than those in the normal group before intervention (<0.01). After intervention, NDS and NBS in the model group were higher than the normal group (<0.01); the two scores were all reduced when compared with those before intervention in the inhibitor group and the ESA group (<0.01), and lower than those of the model group (<0.01). NDS in the ESA group was lower than the inhibitor group (<0.05). In the model group, the cells were shrunk and vacuolated in the ischemic cortical lesion. Many normal cells were visible in the ESA group and the inhibitor group. Compared with the normal group, the concentrations of IL-12 and IL-12R , the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in brain tissue of ischemic cortical lesion were all increased in the model group (<0.01), while the protein expression level of IL-4 decreased (<0.01). The concentrations of IL-12 and IL-12R, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ were all reduced (<0.01), while the protein expression level of IL-4 increased (<0.01) in the ESA group and the inhibitor group when compared with the model group. The concentration of IL-12, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in the ESA group were all higher than those of the inhibitor group (<0.05); while the concentration of IL-12R and the protein expression level of IL-4 were lower than the inhibitor group (<0.05).

CONCLUSION

Electro-scalp acupuncture may improve the neurological function of the rats with ischemic stroke. The modulation to IL-12 mediated JAK/STAT signaling pathway is the potential molecular mechanism of this therapy for the inflammatory response in ischemic cortical lesion.