Regulatory effects of acidic peptide on the levels of N-methyl-D-aspartate receptor, nerve growth factor and beta-amyloid in the brain of rats with Alzheimer disease / 中国组织工程研究

ABSTRACT

BACKGROUND: It has been confirmed that acidic peptide has good therapeutic effect on rat models of Alzheimer disease, but the mechanism still needs further exploration.OBJECTIVE: To observe whether acidic peptide can inhibit the production of N-methyl-D-aspartate receptor (NMDAR) and beta-amyloid (β-amyloid) in brain, and accelerate the production and excretion of nerve growth factor (NGF) in rats with Alzheimer disease.DESIGN: A randomized controlled animal experiment.SETTING: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University.MATERIALS The experiments were finished in the first laboratory of Institute of Bioactive Peptide, Zhengzhou University and the Cellular Culture Center, School of Basic Medical Sciences of Zhengzhou University from March 2005 to May 2006. Seventy 10-week-old healthy male SD rats without dementia symptoms were randomly divided into 7 groups with 10 rats in each group normal control group, model group, saline group, glutamic acid 0.3 g/kg group, acidic peptide 15, 30 and 60 mg/kg groups.METHODS: Except the normal control group, the rats in the other 6 groups were induced into models of Alzheimer disease by damaging bilateral nucleus basalis of Meynert with ibotenic acid, and then intragastric administration of glutamic acid (0.3 g/kg) was given in the glutamic acid 0.3 g/kg group, acidic peptide of corresponding dosages in the acidic peptide 15, 30 and 60 mg/kg groups, and isovolume saline in the saline group respectively, 2 mL for each time, once a day for 20 days continuously.MAIN OUTCOME MEASURES: ① The learning ability of the rats was detected with Y-maze test immediately after the end of intragastric administration, and the times of correct responses were recorded. ② After the end of learning and memory test, the head was cut rapidly to remove brain,treated with immunohistochemical staining, and gray value was scanned with Biosens Digital Imaging System to determine the contents of NMDAR,NGF and β-amyloid in the brain of rats.RESULTS: All the 70 rats were involved in the analysis of results. ①Times of correct responses in the Y-maze test were lower in the other 6groups than in the normal control group (P ＜ 0.01), but higher in the acidic peptide 30 and 60 mg/kg groups than in the model group, saline group, glutamic acid 0,3 g/kg group and acidic peptide 15 mg/kg group (P ＜ 0.01). ②The gray values of NGF in basal forebrain in the model group, saline group,glutamic acid 0.3 g/kg group and acidic peptide 15 mg/kg group were lower than that in the normal control group (69.60±2.41, 69.62±1.46, 69.62±1.46,69.73±1.87, 80.77±2.72, P ＜ 0.01); There were no significant differences between the acidic peptide 30 and 60 mg/kg groups (79.39±2.23, 80.20±1.7, P ＞ 0.05), which were higher than the other groups. ③ The gray values of NMDAR and β-amyloid in cerebral cortex in the model group,saline group, glutamic acid 0.3 g/kg group and acidic peptide 15 mg/kg group were lower than those in the normal control group (NMDAR 81.01±1.38, 81.31±2.06, 81.37±1.39, 79.38±1.23, 69.50±1.04; β-amyloid74.26±1.39, 74.89±8.66, 74.88±1.46, 74.16±2.48, 67.40±3.06, P ＜ 0.01),and There were no significant differences between the acidic peptide 30and 60 mg/kg groups (P ＞ 0.05), which were lower than the other groups.CONCLUSION: Acidic peptide of 30 and 60 mg/kg can obviously ameliorate the learning and memory abilities in rat models of Alzheimer disease, which may be realized mainly through up-regulating the NGF content in basal forebrain and down-regulating the NMDAR and β-amyloid contents in cerebral cortex.