Abstract: BACKGROUND: Electroacupuncture intervention at Quchi (LI11) and Zusanli (ST36) acupoints can play a neuroprotective effect and improve motor function in patients. However, there are relatively few in-depth studies on its mechanism of action.
OBJECTIVE: To investigate the neuroprotective effect of electroacupuncture intervention in a rat model of cerebral ischemia-reperfusion injury based on the neuregulin-1/epidermal growth factor receptor 4 signaling pathway.
METHODS: Ninety specific pathogen-free male Wistar rats were randomly divided into three groups (n=30 per group): a model group, a non-acupoint group, and an acupoint group. Another 30 rats were selected as a sham operation group with the separation of blood vessels in the left side of the neck. At 3 hours after modeling, in the non-acupuncture group, electroacupuncture was performed atthe non-acupoints under the axillary transverse striae of the right limb and 3 mm below the tip of the coccyx by using electroacupuncture, while in the acupuncture group, electroacupuncture was performed at Quchi (LI11) and Zusanli (ST36) acupoints for 7 days. Rats in the sham operation and model groups were not given any treatment, only grasped and fixed under the same conditions as the non-acupoint and acupoint groups. After modeling, the neurological deficit scores were used for model evaluation. The neurological deficit scores were evaluated in each group after treatment; and the regional cerebral blood flow and blood flow velocity on the ischemic side were measured. 2,3,5-Triphenyltetrazolium chloride staining was used to detect the volume of cerebral infarction. Electron microscope was used to observe the ultrastructure of neurons. TUNEL staining was used to detect the apoptosis of neurocytes. Western blot was used to detect the pathway protein expression of neuregulin 1/epidermal growth factor receptor 4.
RESULTS AND CONCLUSION: Compared with the sham operation group, the neurological deficit score, cerebral infarction volume, neuronal apoptosis rate, neuregulin-1 protein level, and epidermal growth factor receptor 4 protein level were significantly increased, cerebral blood flow and cerebral blood flow velocity were significantly decreased in the model and non-acupoint groups (P < 0.05). The ultrastructure of neurons was abnormal in the model group and the non-acupoint group. However, there was no significant difference between the model group and the non-acupoint group (P > 0.05). Compared with the model group, the neurological deficit score, cerebral infarction volume, neuronal apoptosis rate were significantly decreased, and cerebral blood flow, cerebral blood flow velocity, neuregulin 1 protein level, and epidermal growth factor receptor 4 protein level were significantly increased in the acupoint group (P < 0.05). The ultrastructure of neurons was also significantly improved in the acupoint group. These results indicate that electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints can significantly improve the state of neurological deficit and the ultrastructure of brain neurons , inhibit neuronal apoptosis, and play a neuroprotective effect in rats with cerebral ischemia-reperfusion injury. Its mechanism may be related to the regulation of neuregulin-1/epidermal growth factor receptor 4 signaling pathway.

Key words: neuregulin-1, epidermal growth factor receptor 4, electroacupuncture intervention, cerebral ischemia-reperfusion, neuroprotection, apoptosis