高胆固醇膳食诱发去卵巢兔脑内β淀粉样蛋白生成增多

High cholesterol diet increases the deposition of β-amyloid in brains of ovariectomized rabbits

目的初步探讨雌激素、胆固醇与AD之间的关系。方法雌性6月龄新西兰大白兔24只,随机分为正常对照组、假手术高胆固醇膳食组(假手术+2%胆固醇膳食)、去卵巢高胆固醇膳食组(去双侧卵巢+2%胆固醇膳食)。于实验0,4,8,12周动态监测血清总胆固醇浓度、低密度脂蛋白胆固醇浓度、高密度脂蛋白胆固醇浓度及甘油三酯浓度变化;于12周处死动物,取兔脑皮质(额叶、颞叶)进行Aβ免疫组织化学染色。结果喂高胆固醇膳食后,去卵巢高胆固醇膳食组血清总胆固醇浓度、低密度脂蛋白胆固醇浓度、甘油三酯浓度明显高于正常对照组、假手术高胆固醇膳食组(P<0.05);Aβ免疫组织化学染色经图像分析去卵巢高胆固醇膳食组阳性指数(PI)明显高于正常对照组、假手术高胆固醇膳食组(P<0.05)。结论高胆固醇膳食可以诱发雌激素缺乏兔脑内Aβ生成增多;雌激素具有显著的降胆固醇作用,可能是其抑制高胆固醇膳食诱发Aβ生成增多的机制之一。

Objective To investigate the relationship between estrogen, cholesterol and Alzheimer disease （AD）. Methods Twenty four 6-month-old female New Zealand white rabbits were randomly divided into three groups （ n = 8, each group） ： normal control group （NC）, sham-operated and high cholesterol diet group （ SO ＋ HC）, ovariectomized and high cholesterol diet group （OVX＋ HC）. The rabbits in NC group were fed normal rabbit diet, and the rabbits in the other two groups were fed 2% high cholesterol diet for 12 weeks. At week 0,4,8 and 12, serum total cholesterol （TC）, triacylglycerol （TG）, high-density lipoprotein cholesterol （HI）L-C） and low-density lipoprotein cholesterol （LDE-C） were measured. At the end of the experiment, the number and cross area of amyloid beta-protein （Aβ） deposited macula in cerebral cortex were estimated quantitatively using immunohistochemical method and image pattern analysis. Results Serum TC, LDL-C and TG were significantly elevated in OVX ＋HC group compared with SO＋ HC group and NC group （P〈0.05）. Senile-plaques-like structures were observed in temporal lobe and frontal lobe only in HC ＋ OVX group. Less Aβ immunoreactivity was observed in the other groups （ P 〈0. 05）. Conclusion High cholesterol diet increass the deposition of β-amyloid in the brains of ovariectomized rabbits. Estrogen can reduce TC that may be one protective mechanism in the animal model. AD may be prevented or delayed by lowering TC after supplying estrogen.