Effect Of CZ2HF On ?-amyloid 25-35 Fragment-induced Learning And Memory Impairment In Rat

Objective: To investigate the effect of CZ2 HF on the learning and memory impairment model induced by ?-amyloid _25-35(A?_25-35)in rats.Methods: Healthy ninety-night male Sprague-Dawley?SD?rats were randomly divided into 7 groups?n=14 in each group?: sham,sham+CZ2HF?400 mg/kg?,model(A?_25-35),A?_25-35+CZ2HF?100 mg/kg?,A?_25-35+CZ2HF?200 mg/kg?,A?_25-35+ CZ2HF?400 mg/kg?,Donepezil?1.0 mg/kg?group,respectively.Model rats were injected with A?_25-35 5 ?L?2?g/?L?into the bilateral hippocampal,the rats of sham group were injected with volume-matched saline solution,instead.Rats in CZ2 HF low-,medium-,high-dose groups and donepezil group were intragastrically administered with CZ2HF100,200,400 mg/kg,and 1.0 mg/kg once a day for 17 days,while the sham and model group rats were treat with volume-matched vehicle,instead.Morris water maze?MWM?test was applied to evaluate spatial learning and memory ability of rats on day 11-17 after surgery,then the rats were sacrificed.After MWM test,hippocampal neuronal damage and apoptosis of rats were observed by HE staining,Nissl staining and TUNEL assays.The protein expression of TNF-?,IL-1?,COX-2,I?B-?,Bax,Bcl-2,pro-caspase 3;the protein level of A?1-42 ?active-caspase 3 and NF-?B p65 phosphorylation were analyzed by western blot,respectively.Results: Compared with the sham group,the mean escape latency was dramatically increased,time percentage in the target quadrant were markedly decreased in model group;the hippocampal neurons of CA1 region arranged in disorder,cells were degenerated,the number of surviving neurons were decreased and the number of apoptasis cell were increased;the protein expression of TNF-?,IL-1?,COX-2,Bax were enhanced,the protein levels of A?1-42,active-caspase3 were increased;the levels of NF-?B p65 Phosphorylation were enhanced,the protein levels of I?B-?,Bcl-2,pro-caspase3 were reduced.However,compared with the model group,the escape latency of CZ2 HF and positive drug groupswas shorter,time percentage in the target quadrant were markedly increased in CZ2HF-treated rats;hippocampal neurons arranged with regular,structure was complete,the number of surviving neurons was significantly increased and apoptosis cell was reduced;the protein expression of TNF-?,IL-1?,COX-2 were significantly decreased;the protein levels of A?1-42,,active-caspase3 were reduced;the protein expression of I?B-?was increased;Bax/Bcl-2 ratio and the NF-?B phosphorylation level were significantly reduced.These effects in sham CZ2HF-treated group showed no notable differences compared to the sham group.Conclusion: Under the experimental conditions,CZ2 HF significantly improves A?_25-35-induced learning and memory impairment and hippocampal neuronal injury,the mechanism may be due to anti-inflammatory,anti-apoptosis.