Abstract: BACKGROUND: The mechanisms underlying the protection of electroacupuncture against cerebral ischemia/reperfusion injury in rats and its temporal efficacy have been less studied in the past.
OBJECTIVE: To observe the effect of electroacupuncture on the expression of p-ERK, p-JNK and p-p38MAPK proteins in three signaling pathways of the MAPK family in rats with cerebral ischemia/reperfusion at different times, and to explore the specific mechanism underlying the cerebral protection of electroacupuncture.
METHODS: 150 Sprague-Dawley male rats were randomly divided into sham-operated group, model group, and electroacupuncture group, with 50 rats in each group. Each group was then set up for ischemia 1.5 hours followed by reperfusion for 2 hours, 6 hours, 1 day, 3 days, and 7 days, with 10 rats in each subgroup. Single electroacupuncture treatment at Hegu, Shakuze, Zusanli, and Sanyinjiao was conducted at the given time, giving sparse waves at a frequency of 2 Hz, intensity of 1 mA, 20 minutes for one session. Rats in the model and sham-operated groups were grasped simultaneously for fixation at the same time of electroacupuncture, but no electroacupuncture intervention was performed. After anesthesia, the brains were decapitated at the corresponding time points, and neurological deficit scoring was used to observe the infarct area by TTC staining. The expression of p-ERK, p-JNK, and p-p38MAPK was detected by double immunofluorescence labeling method.
RESULTS AND CONCLUSION: Compared with the sham-operated group, the model group had higher neurological deficit scores and larger infarct size in each subgroup in the same period (P < 0.05). Compared with the model group, there were significantly lower neurobehavioral scores and smaller infarct size in the electroacupuncture subgroups of 6 hours, 1 day and 3 days (P < 0.05). Compared with the model group, the electroacupuncture group had significant up-regulation of p-ERK expression at 1 and 3 days of reperfusion (P < 0.05), downregulation of p-JNK expression at 1 and 3 days of reperfusion (P < 0.05), and significant downregulation of p-p38MAPK expression at 6 hours and 3 days of reperfusion (P < 0.05). To conclude, electroacupuncture can reduce infarct size, alleviate neurological deficits, up-regulate p-ERK expression and down-regulate the expression of p-JNK and p-p38MAPK at the same time. The best effect of electroacupuncture is within 6 hours-3 days. Electroacupuncture promotes the repair of brain tissue damage caused by cerebral ischemia/reperfusion and exerts cerebral protection through the regulation of MAPK family signaling pathway.

Key words: electroacupuncture, cerebral ischemia/reperfusion, MAPK signaling pathway, cerebral infarction, rat