The Effect Of Electro-accupuncture And Nimodipine On The Expression Of Hippocampus Caαnachr In AD Rats

Objective To observe the changes of behavior,α7nAchR-immunoreactive cells andα7nAchR protein in the hippocampus between control and model group.To observe the changes of behavior ,α7nAchR-immunoreactive cells andα7nAchR protein in the hippocampus with electro-accupuncture, nimodipine or both of them after 2 weeks, 4weeks, 6 weeks.Study the underlying mechanism of electro-accupuncture and nimodipine on learning and memory.Methods 210 healthy male Sprague-Dawley rats selected by water maze place navigation testing , divided into seven groups randomly, including control group, model group, nimodipine treatment group, EA group, combined treatment group, EA non-accupoint group, donepezil group. Rats in each group were observed after 2 weeks, 4 weeks, 6 weeks, each observation point has 10 rats.Except control group, the other six groups were injected D-galactose 60mg/kg .d into intraperitoneal for 6 weeks. The rats of control group were injected with normal saline at corresponding time. 7 days later, 3Hz, 1-2 mA , density wave electro-accupuncture treatment was used in rats of EA group,nimodipine 0.25mg / d intravenous injection was used in rats of nimodipine treatment group,combination therapy of the two methods was used in rats of combined treatment group,the same stimulation parameter as EA group was used in rats of EA non-accupoint group but stimulation site is muscle tissue 5mm next to the accupuncture points without meridian passing by,donepezil 0.125 mg / d intragastric administration was used in rats of donepezil group.The treatment time of three groups in each major group was 2 weeks, 4 weeks, 6 weeks, Rats in every group were drawn at corresponding time point.α7nAchR immunoreactive cells were detected by SP immunohistochemistry,the whole hippocampusα7nAchR protein were detected by western blotting.Results1. Compared with control rats at 2 weeks, 4 weeks, 6 weeks, the escape latency of D-galactose-induced AD rats was significantly longer (P<0.01), the number of cross-platform after dropping the platform was significantly reduced (P<0.05), the percentage of target quadrant time was significantly reduced (P<0.01) and search strategy has changed (P<0.01). Compared with model rats at 4 weeks, the escape latency of EA group was significantly shorten (P<0.01), the number of cross-platform after dropping the platform was significantly increased (P<0.05) and the percentage of target quadrant time was significantly increased (P<0.01), search strategy of EA group has changed at 6 weeks, The escape latency of nimodipine treatment group was significantly shorten (P<0.01), the number of cross-platform after dropping the platform was significantly increased (P<0.05) and the percentage of target quadrant time was significantly increased (P<0.01), search strategy has changed at 6 weeks; 2. The number of cross-platform after dropping the platform was significantly reduced in nimodipine treatment group at 4 weeks (compared with 2 weeks and 6weeks, P<0.05) and the percentage of target quadrant time was significantly reduced (compared with 2 weeks and 6 weeks, P<0.05). 3.α7nAchR immunoreactive cells in the hippocampal CA₃ area of control group were large in size, stained deeply, regular and massed. Positive cells in model group were stained lightly and rare, EA group has no significant change at 2 weeks, stained cells were deepened with an increased number at 4 weeks, cell number and size were significantly increased at 6 weeks. Stained cells of nimodipine treatment group were deepened with increased number at 2 weeks, while shape is irregular, shallow with smaller size and morphology disorder at 4 weeks, deep-staining and regular at 6 weeks. 4. Expression ofα7nAchR protein in the hippocampus has increased in EA group at 4 weeks, 6 weeks, in nimodipine treatment group at 2 weeks, 6 weeks and increased in combined treatment group (P<0.01) at 2 weeks, 4weeks, 6 weeks, there was no significant difference between combined treatment group and control group at 2 weeks, 4weeks, 6 weeks (P>0.05).Conclusions1.α7nAchR in hippocampus CA₃ has a relationship with rat spatial learning and memory.2. Electro-accupuncture and nimodipine can improve rat spatial learning and memory by increasingα7nAchR in hippocampus CA₃. 3. The effect of nimodipine on rat spatial learning and memory has an interaction.