Expression Of Bcl-2, Bax In Hippocampus With Aβ_1-40 Induced Alzheimer's Disease Rat Models And Its Intervention Study

Objective: To establish rat models with Alzheimer's disease(AD) induced byβ-Amyloid1-40, and to observe the effects of Fastigial nucleus stimulation(FNS)on spatial memory and learning ability of the rats, and the expression of Bax, bcl-2 in hippocampus area.Method: Forty male SD rats were selected and randomly divided into 4 groups including the sham group(SC group), the Alzheimer group(AD group), the Alzheimer group with a FNS treatment(FNS group)and the Alzheimer group with a DNS treatmen(tDNS group), in which Aβ1-40 was microinjected into CA1 subfield in the right hippocampus to induce the Alzheimer disease rat models and cerebellar dentate nucleus and fastigial nucleus were stimulated separately before the model was made.The spatial memory and learing ability of the rat was evaluated by the Morris water maze procedure in the 28th day after the injection. The pathology variety of neurons in hippocampus was observed by HE staining method.The expression of bcl-2, Bax in hippocampus were detected by RT-PCR and immunohistochemistry analysis. Results:(1)The escape latency of the place navigation of the AD group was singnificiantly longer than the sham injection group(p<0.05); The AD rats received FNS showed significiante shorter escape latency than AD rats(p<0.05).Dentate nucleus stimulation showed no such effect(p>0.05).(2) The optical density mean of positive cells of bcl-2 in hippocampus area of SC group was 0.27±0.05, the optical density mean of positive cells of bcl-2 in hippocampus area of AD group(0.20±0.04)was significant lower than SC group, the optical density mean of positive cells of bcl-2 of FNS group(0.37±0.10)was higher than SC and AD group(p<0.05). However, there was no significant difference in DNS group(0.19±0.04) and AD group(.P>0.05)The optical density mean of positive cells of Bax in hippocampus area of SC group was 0.26±0.06, the optical density mean of positive cells of Bax in hippocampus area of AD group(0.67±0.06)was significant higher than SC group, the optical density of positive cells of bcl-2 of FNS group (0.43±0.07)was higher than SC group but lower than AD and DNS group(p<0.05). However, there was no significant difference in DNS group(0.68±0.09)and AD group(P>0.05).(3) The expression levels of bcl-2 mRNA in hippocampus were significantly decreased in AD(0.1938±0.0087) and DNS(0.1938±0.0136) group compared to the SC group(0.3153±0.0110)(p<0.05),the AD rats received FNS showed significiante higher expression of bcl-2 mRNA in hippocampus(0.3823±0.0158) than other rats(p<0.05); Secondly, the result showed the expression levels of Bax mRNA in the hippocampus were significantly increased in AD ( 0.5843±0.0145 ) , DNS (0.5682±0.0101)and FNS treatment group(0.3950±0.0070) in contrast to SC group(0.3505±0.0072), the AD rats received FNS showed significiante lower expression of Bax mRNA in hippocampus than AD rats(p<0.05), dentate nucleus stimulation showed no such effec(tp>0.05).Conclusions: Together, these results showed that FNS can partly improve the spatial learning and memory dysfunction of AD rat, it can inhibit apoptosis and has neuroprotective effect of hippocampal cells by inhibit the expression of Bax and promote the expression of bcl-2 of hippocampus area.