Objective: To investigate the effect of electroacupuncture (EA) on the p38 mitogen-activated protein kinase (p38 MAPK) and signal transducer and activator of transcription 3 (STAT3) pathway in hippocampus and frontal cortex of diabetic rats with cognitive impairment (CI), as well as the mechanism of EA in protection against CI in diabetic rats.
Methods: Thirty SD rats were divided into normal, model and EA groups (n=10 rats/group). The diabetic model was established by i.p.injection of Streptozotocin solution(25 mg/kg), followed by high-fat diet raising for 1 month, and the CI rats was confirmed by Morris water maze tasks. The rats in the EA group were given acupuncture at "Zusanli" (ST36) "Neiting" (ST44) and "Yishu" (EX-B3) 20 min/d, among which ST36 and ST44 were treated with EA. The treatment was conducted 6 times a week for 4 weeks. The fasting blood glucose (FBG) contents were assayed by glucometer before and after treatment. The rats' learning-memory ability was detected by Morris water maze tasks. The expression levels of IL-6、IL-1β、TNF-α、p38 MAPK、p-p38 MAPK、STAT3 and p-STAT3 in hippocampus and frontal cortex were detected by Western blot and quantitative real-time PCR, separately. The mean fluorescence intensity of p38 MAPK and STAT3 was observed by immunofluorescence histochemistry.
Results: After modeling, FBG and the escape latency of Morris water maze tasks were significantly increased in the model group compared with the normal group (P<0.001, P<0.01). Following EA treatment, the increased FBG and average escape latency were markedly reversed in the EA group relevant to the model group (P<0.05). Compared with the normal group, the proteins and mRNAs expression of IL-6, IL-1β, TNF-α, p38 MAPK, p-p38 MAPK, STAT3 and p-STAT3 in hippocampus and frontal cortex were significantly increased in the model group (P<0.001), as well as the mean fluorescence intensity of p38 MAPK and STAT3 in hippocampus and frontal cortex (P<0.001). Following EA intervention, the proteins and mRNAs expression of IL-6, IL-1β, TNF-α, p38 MAPK, p-p38 MAPK, STAT3 and p-STAT3, and the mean fluorescence intensity of p38 MAPK and STAT3 in hippocampus and frontal cortex were down-regulated(P<0.001, P<0.05).
Conclusion: EA can inhibit the over production of pro-inflammatory cytokines in diabetic rats with CI, possibly by regulating the expression of p38 MAPK and STAT3 pathway.
Keywords: Diabetic rats with cognitive impairment; Electroacupuncture; Inflammatory factor; STAT3; p38 mitogen-activated protein kinase.