| Objective: Alzheimer's disease is a neurodegenerative disease that occurs in the elderly population,which seriously reduces the quality of life of the elderly.Currently,the treatment of drugs can only delay the progression of the disease,and it cannot completely cure the disease,and its side effects are large.Because of its special structure and its special physical and chemical properties and functions,marine drugs are proposed to investigate the neuroprotective effect of peracetylated chitosan oligosaccharide on A?-induced SD rat injury and the possible mechanism of Alzheimer's disease.Methods: One hundred healthy male SD rats of SPF grade were randomly selected as sham operation group,and the other 80 were injected with 5?L A?25-35(4?g/?L)according to stereotaxic pattern of rat brain under brain stereotaxic apparatus as AD model.The 71 rats after successful modeling were randomly divided into four groups: model,low,medium and high all-acetylated chitosan oligosaccharides.On the 8th day after model establishment,the stomach was administered and the stomach was continuously administered for 21 days.The sham operation group and the model group were given corn oil 5ml/kg,and the peracetylated chitosan oligosaccharides were formulated into three concentrations of low(5 mg/m L),medium(10 mg/m L)and high(20 mg/m L).The intragastric dose was low dose group(25 mg/kg·d),middle dose group(50 mg/kg·d),high dose group(100 mg/kg·d).Rat body weight was recorded during gavage.After the end of the test,the rats were perfused and the brain tissue and hippocampus were taken.The contents of malondialdehyde(MDA),lactate dehydrogenase(LDH)and superoxide dismutase(SOD)in brain tissue were detected by kit,and Tau protein(Tau),interleukin-6(IL-6)and the content of tumor necrosis factor alpha(TNF-?)were detected by ELISA.Morphological changes of rat hippocampus were observed by HE staining.Immunohistochemical staining and Westeern blot were used to detect the expression levels of p-caspase3,p-cytochrome C,p-ERK1/2,p-PI3 K,p-Akt2 and p-GSK3? in hippocampus.Results: Compared with the control group,after the injection of A?25-35 into the lateral ventricle of the model group,the escape latency increased,the escape latency increased compared with the control group,the target quadrant dwell time and the number of crossing platforms decreased,and the SOD content in the brain decreased,LDH,MDA,TNF-?,IL-6,The content of Tau and Aa increased,the damage of hippocampal neurons was obvious,and a large number of cell necrosis and even vacuoles were observed.The expression of pcaspase3,p-cytochrome C,p-ERK1/2,p-PI3 K and p-Akt2 increased compared with the control group.(P<0.05),p-GSK3? expression was lower than the control group(P<0.05).After the PACOS treatment,the escape latency of the rats decreased compared with the model group,the target quadrant residence time and the number of crossing platforms increased,the SOD content in the brain tissue increased,and the contents of LDH,MDA,TNF-?,IL-6,Tau,Aa decreased.The tissue neuron injury was significantly improved.The expression of p-caspase3,p-cytochrome C,p-ERK1/2,p-PI3 K and p-Akt2 was lower than that of the model group(P<0.05),and the expression of p-GSK3? was increased compared with the model group(P< 0.05).Conclusion: The neuroprotective effect of peracetylated chitosan oligosaccharide may be closely related to its anti-inflammatory,anti-oxidative stress and inhibition of PI3 K / AKT2 / GSK3 signaling pathway to promote A?-induced neuronal damage repair and inhibition of neuronal apoptosis.It is suggested to have a therapeutic effect on A?25-35-induced Alzheimer's disease. |
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