Effect of electroacupuncture on neurological function and Wnt signaling pathway in ischemic brain tissue of cerebral infarction rats

Objective To explore the mechanism of electroacupuncture(EA) underlying improvement of cerebral infarction(CI) by investigating its influence on expression of cerebral Wnt7 a, lymphoid enhancer factor-1(LEF1), glycogen synthase kinase 3β(GSK-3β) and Dickkopf-1(DKK1) mRNA and proteins in CI rats. Methods A total of 280 male Wistar rats were randomly divided into blank control(n=10), sham-operation, model and EA groups,and 90 rats of the last 3 groups were further divided into 1, 3, 6, 9, 12 and 24 h, and 3, 7 and 12 d subgroups with 10 rats in each subgroup. The CI model was established by occlusion of the middle cerebral artery(MCAO). The sham-operation group received the same surgical operation but without thread embolus insertion. EA(2 Hz/15 Hz, 2 mA) was applied to "Shuigou"(GV26) for 20 min, once a day for 1, 3, 7 and 12 d, respectively. The neurological deficit was evaluated by using Neurological Severity Scores(NSS). The expression levels of Wnt7 a,LEF1, GSK-3β and DKK1 mRNAs and proteins in the right ischemic brain tissues were detected by Quantative real-time PCR and Western blot, respectively. Results After MCAO, the NSS score was significantly increased in the model and EA groups relevant to the blank control and sham-operation groups(P<0.01) and gradually decreased with the prolongation of ischemia time. After EA, the NSS scores were notably decreased on day 3, 7 and 12 in the EA group compared with the model group(P<0.05, P<0.01). After modeling, the expression levels of Wnt7 a and LEF1 mRNAs from 3 h to 12 d, Wnt7 a and LEF1 proteins from 6 h to 12 d were considerably increased(P<0.01, P<0.05), while those of GSK-3β mRNA at 9, 12 and 24 h, GSK-3β protein at 24 h and 3 d, and DKK1 mRNA at 24 h and 3 d and DKK1 protein at 3 d were obviously decreased in the model group relevant to the sham-operation group(P<0.05, P<0.01). After the intervention, the expression levels of Wnt7 a mRNA at 12 h to 3 d, Wnt7α protein from 24 h to 12 d, LEF1 mRNA from 24 h to 12 d, and LEF1 protein from 3 d to 12 d were further apparently up-regulated(P<0.01, P<0.05), while those of GSK-3β mRNA at 9 h, 3,7 and 12 d, and GSK-3β protein at 12 h, 7 d and 12 d, and DKK1 mRNA at 12 h, 24 h and 3 d, and DKK1 protein at 24 h to 12 d were obviously down-regulated in the EA group relevant to the model group(P<0.01, P<0.05). No significant difference was found between the blank and sham-operation groups in the NSS scores and expression levels of Wnt7 a, LEF1, GSK-3β and DKK1 mRNAs and proteins at all the time points(P>0.05). Conclusion EA of GV26 can significantly improve the neurological deficit symptoms in MCAO rats, which may be associated with its effects in up-regulating the expression of Wnt7 a and LEF1 mRNAs and proteins, and in down-regulating the expression of GSK-3β and DKK1 mRNAs and proteins.