Objective To explore the neuroprotective effect and related mechanism of electroacupuncture (EA) combined with tanshinone Ⅱ A (Tan Ⅱ A) for the treatment of rats with cerebral ischemia-reperfusion (I/R) injury.

Methods Model rats with cerebral I/R were established by the modified Longa suture occlusion method and randomly divided into Model group, EA group, Tan Ⅱ A group, and EA+Tan Ⅱ A group, with 16 rats in each group. Rats in the Sham group (n=16) had their carotid arteries exposed and dissected but not occluded. Neurological deficit score and Morris water maze test were used to assess neurological impairment and cognitive function in rats. 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to evaluate cerebral infarction volume. Hematoxylin-eosin (HE) staining and TUNEL staining were used to assess neuronal damage in the hippocampus. Western blot was used to detect apoptosis-related proteins and proteins related to the Hippo signaling pathway.

Results Compared with the Sham group, the Model group showed increased neurological deficit score, percentage of cerebral infarction area, escape latencies during acquisition training, proportion of TUNEL-positive stained cells in brain tissue, Caspase-3 activity, expression of Cleaved Caspase-3 protein and Bax protein, and decreased expression of time spent in the target quadrant during probe training, the number of platform crossings within 60 s, Bcl-2 protein, Yes-associated protein (YAP), and transcriptional co-activator with PDZ-binding motif (TAZ) protein, and all the differences were significant (P < 0.05).Compared with the Model group, the EA group, Tan Ⅱ A group, and EA+Tan Ⅱ A group showed decreased neurological deficit score, percentage of cerebral infarction volume, escape latencies during acquisition training, time spent in the target quadrant during probe training, number of platform crossings within 60 s, proportion of TUNEL-positive stained cells in brain tissue, Caspase-3 activity, expression of Cleaved Caspase-3 protein and Bax protein, with the EA+Tan Ⅱ A group showing lower values than the EA group and Tan Ⅱ A group, and all the differences were significant (P < 0.05). Compared with the Model group, the EA group, Tan Ⅱ A group, and EA+Tan Ⅱ A group showed increased expression of Bcl-2, YAP, and TAZ proteins, with the EA+Tan Ⅱ A group showing higher protein expression levels than the EA group and Tan Ⅱ A group, and all the differences were significant (P < 0.05).

Conclusion The combination of EA and Tan Ⅱ A for the treatment of cerebral I/R injury exhibits synergistic effect, and its mechanism may be related to the inhibition of Hippo pathway activity.