Study On Alzheimer's Disease-like Pathological Changes Induced By High Cholesterol Diet In The OVX Rabbit And The Protection Of Estrogen

Objective: To establish a high cholesterol diet animal model of Alzheimer's disease (AD) in the estrogen deficiency rabbit and to observe the effect of estrogen on patho-morphological parameters and some other relative index of AD(serum lipid, β-amyloid, free radicals)in the model, to explore the estrogen protection to AD model rabbit induced by high cholesterol diet. Materials and Methods: Thirty-two 6-mouth-old female New-Zealand rabbits were randomly divided into three groups (n=8 for each group), normal control (NC) group, sham-operated and high cholesterol diet group (SO+HC), oophoretomy and high cholesterol diet group (OVX+HC). OVX+HC group were treated with oophoretomy; all groups except NC group were fed with high cholesterol for 12 weeks. At week 0, 4, 8 and 12, the serum lipid TC, TG, HDL-C, LDL-C, beta-amyloid (Aβ), SOD and MDA were measured. At feeding cholesterol week 12, the number and cross area of Aβdeposited macula in cerebral cortex and hippocampus were estimated quantitatively using immunohistochemical method and image pattern analysis. the expression of APPmRNA in cerebral cortex and hippocampus were estimated quantitatively using RT-PCR method. Results: Serum TC, LDL-C,TG,HDL-C and Aβlevel obviously increase in HC+OVX group as compared with NC group.Estrogen can decrease TC, LDL-C,TG,HDL-C and Aβinduced by high cholesterol diet in ovariectomized rabbits.there were no markable effect of estrogen on serum HDL-C. There was significantly decrease of SOD and GPX activity in HC+OVX group and estrogen can suppression of SOD and GPX activity andobviously increase of serum MDA in HC+OVX group. Estrogencan enhance antioxidant defenses and reduce oxidant insult. Sps-like structure were observed in hippocampus, temporal lobe, frontal lobe only in HC+OVX group. Less Aβimmunoreactivity was observed in the other group (P <0.05). The APPmRNA in HC+OVX group was overexpressed as compared with NC and SO+HC group. Conclusion: 1.High cholesterol diet can induce AD-like pathological changes in the estrogen deficiency rabbit which is a good animal model for AD. 2. Estrogen can decrease serum TC LDL-C,TG..3. Estrogen can inhibit the production of Aβand the overexpress of APPmRNA in the AD model rabbit induced by high cholesterol diet. 4. High cholesterol diet can increase of serum MDA and suppress the activity of SOD and GPX .There was significantly decrease of SOD and GPX activity. Estrogencan enhance antioxidant defenses and reduce oxidant insult. 5.Estrogen can inhibit the overexpression of APPmRNA. 6.All these suggest :after menopause women with high cholesterol diet will be liable to AD ,that may controbite to the loss of estrogen for cholesterol metabolism.