Effect Of CZ2HF On β-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 β-amyloid _25-35(Aβ_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(Aβ_25-35),Aβ_25-35+CZ2HF（100 mg/kg）,Aβ_25-35+CZ2HF（200 mg/kg）,Aβ_25-35+ CZ2HF（400 mg/kg）,Donepezil（1.0 mg/kg）group,respectively.Model rats were injected with Aβ_25-35 5 μL（2μg/μL）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-α,IL-1β,COX-2,IκB-α,Bax,Bcl-2,pro-caspase 3;the protein level of Aβ1-42 、active-caspase 3 and NF-κB 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-α,IL-1β,COX-2,Bax were enhanced,the protein levels of Aβ1-42,active-caspase3 were increased;the levels of NF-κB p65 Phosphorylation were enhanced,the protein levels of IκB-α,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-α,IL-1β,COX-2 were significantly decreased;the protein levels of Aβ1-42,,active-caspase3 were reduced;the protein expression of IκB-αwas increased;Bax/Bcl-2 ratio and the NF-κB 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 Aβ_25-35-induced learning and memory impairment and hippocampal neuronal injury,the mechanism may be due to anti-inflammatory,anti-apoptosis.