[Moxibustion Improves Learning Ability by Regulating Hippocampal Neurotrophic Factor Expression and Notch Signaling in Vascular Dementia Rats].

Objective: To observe the effect of moxibustion on the learning ability and expression of neurotrophic factors and Notch signaling in vascular dementia (VD) rats, so as to explore its neurogenesis mechanism underlying improvement of VD.

Methods: Sixty SD rats were equally and randomly divided into sham operation (sham), model, medication and moxibustion groups (=15 rats/group). The VD model was established by occlusion of the bilateral cervical common arteries and reperfusion. Moxibustion was applied to "Dazhui"(GV 14), "Guanyuan"(CV 4) and "Mingmen"(GV 4)for 15 minutes, once daily, 6 times a week for 4 weeks. Rats of the medication group were treated by gavage of nimodipine (2 mg·kg·d),3 times a day, 6 days a week for 4 weeks. Morris water maze tests were performed to detect the rat's learning-memory ability. The infarcted size of the brain was detected by using 2,3,5-triphenyltetrazolium chloride (TTC) staining, and H.E. staining was used to detect the histopathological changes. The expression level of glia fibrillary acidic protein (GFAP), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), Notch 1 (a receptor), Hes 3 (a downstream effector) mRNAs and proteins in the hippocampal tissues were detected by quantitative real-time PCR and Western blot, respectively.

Results: After 4 weeks' intervention, modeling-induced increase of escape latency was significantly shortened in both moxibustion and medication groups relevant to the model group (<0.05), and the infarct size was reduced and the damage degree of nerve cells in the brain tissue alleviated. The expression levels of BDNF, NGF, GFAP, Hes 3, Notch 1 genes and proteins were significantly up-regulated in the model group relevant to the sham operation group (<0.05,<0.01). After the intervention, the expression levels of hippocampal BDNF, NGF, GFAP, Hes 3 and Notch 1 mRNAs and proteins in the moxibustion group, and NGF and GFAP mRNAs, and BDNF, NGF, GFAP, Hes 3 and Notch 1 proteins in the medication group were further obviously up-regulated relevant to the model group (<0.05, <0.01). The effect of moxibustion was significantly superior to that of medication in up-regulating GFAP, Hes 3, Notch 1 mRNAs expression (<0.05,<0.01). No significant differences were found in the expression of BDNF, Hes 3 and Notch 1 mRNAs in the medication group relevant to the model group (<0.05), and between the moxibustion and medication groups in up-regulating the expression of BDNF and NGF mRNAs, and in up-regulating the expression of BDNF, NGF, GFAP, Hes 3 and Notch 1 proteins (<0.05).

Conclusions: Moxibustion can improve learning ability in VD rats, which may be associated with its effects in up-regulating the expression of neurotrophic factors and in potentiating Notch signaling.