Studies On Alzheimer's Disease-like Pathological Changes Induced By High Cholesterol Diet In Ovariectomized Rabbits And The Protection Of Phytoestrogen

Objective: To establish an animal model of Alzheimer's disease (AD) with high cholesterol diet in the estrogen-deficient rabbit. To comparing patho-morphological parameters and some other relative index of AD(serum lipid, β-amyloid, free radicals) and to observe the effect of phytoestrogen on the AD animal model. Materials and Methods: Thirty-two 6-month-old female New Zealand white rabbits were randomly divided into four groups (n = 8, each group), normal control (NC) group, sham-operated and high cholesterol diet group (SO+HC), ovariectomy and high cholesterol diet group (OVX + HC); ovariectomy, high cholesterol diet and isoflavones group (OVX + HC + Isoflavones). OVX+HC group and OVX + HC + Isoflavones group were treated with ovariectomy. The NC group was fed with normal rabbit chow, the other group was fed with 2% high cholesterol diet for 12 weeks. We also fed OVX + HC + Isoflavones group isoflavones (500mg/kg·d). At week 0, 4, 8 and 12, serum TC, TG, HDL-C, LDL-C, beta-amyloid (Aβ), SOD and MDA were measured. At the end of the experiment, the number and cross area of Aβdeposited macula in cerebral cortex and hippocampus were estimated quantitatively using immunohistochemical method and image pattern analysis. Results: Serum TC, LDL-C, TG, HDL-C and Aβwere significally elevated in OVX+HC group as compared with NC group. Isoflavones can decrease TC, LDL-C, TG and Aβinduced by cholesterol enriched diet in ovariectomized rabbits. There was no markable effect of isoflavones on serum HDL-C. There was significantly suppression of SOD activity and obviously increase of serum MDA in HC+OVX group. Isoflavanones can enhance antioxidant defenses and reduce oxidant insult. Sps-like structures were observed in hippocampus, temporal lobe, frontal lobe only in HC+OVX group. Less Aβimmunoreactivity was observed in the other group (P < 0.05). Conclusion: 1. High cholesterol diet can induce AD-like pathological changes in the estrogen -deficient rabbit which is a good animal model for AD. 2. Phytoestrogen can decrease TC, TG, LDL-C and inhibit the production of Aβ. 3. High cholesterol diet can increase serum MDA and suppress SOD activity. Isoflavones can enhance antioxidant defenses and reduce oxidant insult. 4. Phytoestrogen can display protection of the AD model rabbit induced by high cholesterol diet. Isoflavones have less protection than estrogen. 5. All these suggest: After menopause women with high cholesterol diet will be liable to AD, which may controbite to the loss of estrogen protection against cholesterol metabolism.