Electroacupuncture plus Gastrodin Improves Learning-memory Ability Possibly by Up-regulating Expression of SIRT 1 and PGC-1 ɑ in Hippocampal CA 1 Region of Alzheimer's Disease Rats / 针刺研究

ABSTRACT

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with Gastrodin on learning-memory ability and expression of silent information regulator 2 homologous protein 1(SIRT 1) and peroxisome proliferator activated receptor γ coactivator (PGC-1 ɑ) of hippocampal CA 1 region in Alzheimer's disease(AD) rats, so as to explore its mechanism under-lying improvement of AD. METHODS: Sixty male SD rats were randomly divided into normal control (normal), sham operation (sham), model, EA, Gastrodin and EA＋ Gastrodin groups (n＝10 in each). The AD model was established by intraperitoneal injection of D-Galactose (120 mg•kg－1•d－1) combined with bilateral hippocampal injection of β amyloid 1-40(Aβ 1-40). EA was applied at "Baihui"(GV 20), "Dazhui"(GV 14) and "Zusanli"(ST 36) for 30 min, once daily for 4 weeks. For rats of the Gastro-din group and EA＋ Gastrodin group, intraperitoneal injection of gastrodin(10 mg/kg) was conducted once daily for 4 weeks. Morris water maze tests were used to assess the rat's learning-memory ability. Nissl staining was used to assess the morphological changes of neurons in the hippocampal CA 1 area. The expression of SIRT 1 and PGC-1 ɑ of hippocampal CA 1 region was mea-sured by immunohistochemical staining. RESULTS: 1) Morris water maze tests showed that, compared with the normal and sham group, the escape latency was significantly prolonged (P<0.05), and the percentage of platform quadrant residence duration and the platform crossing times were considerably decreased in the model group (P<0.05). After the intervention, the escape latency was obviously shortened (P<0.05), and the percentage of platform quadrant residence duration and the platform crossing times were markedly increased in the EA, Gastrodin and EA＋Gastrodin groups relevant to the model group (P<0.05). 2) Nissl staining showed that, in comparison with the normal group or sham group, the number of cells in the hippocampal CA 1 area was decreased and the arrangement was disorganized in the model group. The number of cells in CA 1 area was relatively higher in the 3 treatment groups than in the model group. 3) The expression levels of SIRT 1 and PGC-1 ɑ proteins in the hippocampal CA 1 area were significantly down-regulated in the model group than in the normal and sham groups (P<0.05). After the intervention, the expression levels of SIRT 1 and PGC-1 ɑ in the EA, Gastrodin and EA＋Gastrodin groups were significantly up-regulated compared with the model group (P<0.05). The effects of EA＋Gastrodin were significantly superior to those of simple EA and simple Gastrodin in shortening the escape latency, up-regulating the expression levels of SIRT 1 and PGC-1 ɑ as well as in increasing the percentage of platform quadrant residence time and platform crossing times (P<0.05). CONCLUSION: Both EA and Gastrodin can improve the learning-memory ability of AD rats, which may be related to their effects in up-regulating the expression of SIRT 1 and PGC-1 ɑ and reducing neuronal injury in the CA 1 region of hippocampus, suggesting a protective role of EA on hippocampal neurons. The effect of EA combined with Gastrodin is markedly better than that of EA and Gastrodin alone.