高胆固醇血症在阿尔兹海默病发生中的作用及藏药柳茶提取物的治疗效应  

The Role of Hypercholesterolemia in the Outbreak of Alzheimer′s Disease and the Treatment Effect of Sibraea angustata Extract

作　　者：孙雯雯[1] 颉宾芳[1] 刘卉[2] 刘昕[1] 

机构地区：[1]兰州大学基础医学院病理与病理生理教研所,甘肃兰州730000 [2]甘肃中医学院附属医院,甘肃兰州730000

出　　处：《中药材》2012年第4期596-602,共7页Journal of Chinese Medicinal Materials

摘　　要：目的:观察高胆固醇血症在阿尔兹海默病(AD)发生中的作用及藏药柳茶提取物的疗效。方法:SD大鼠随机分为:Ⅰ正常对照组、ⅡAD模型组、Ⅲ高胆固醇血症合并AD组、Ⅳ柳茶治疗组。观察动物一般情况;检测血清和脑组织匀浆中总胆固醇含量;观察海马及皮层组织神经元纤维缠结、β淀粉样蛋白沉积及神经元丢失情况;检测脑组织中胆固醇代谢关键酶APOE、CYP46a1的表达及tau蛋白磷酸化水平。结果:Ⅳ组动物精神状态显著好于Ⅱ、Ⅲ组。Ⅱ组血清胆固醇含量与正常对照组无显著性差异,Ⅲ组显著高于Ⅱ组(P<0.05);Ⅳ组含量低于Ⅲ组。与Ⅰ组相比Ⅱ、Ⅲ组脑胆固醇含量显著升高,Ⅲ组更为明显;柳茶治疗后Ⅳ组脑胆固醇水平下降,与Ⅲ组相比有显著性差异(P<0.05)。Ⅱ组APOE mRNA表达量增加,与Ⅰ组相比P<0.01,而Ⅲ组表达量高于Ⅱ组,Ⅳ组表达量则下降至接近正常水平。Ⅱ、Ⅲ组CYP46a1mRNA表达量均显著少于正常对照组(P<0.01),经柳茶治疗后Ⅳ组表达量显著升高(P<0.01)。与Ⅰ组相比Ⅱ、Ⅲ组tau磷酸化水平升高,尤以Ⅲ组更为明显,Ⅳ组则有所降低。结论:高胆固醇血症能促进AD的发生发展,柳茶提取物可有效降低AD动物血和脑中胆固醇含量,改善脑组织中病理形态学变化。其作用机制可能与调节APOE和CYP46a1mRNA的表达有关。Objective ：To observe the role of hypercholesterolemia in the outbreak of Alzheimer＇ s disease （AD） and the treatment effect of Sibraea angustata extract. Methods：Divided rats into four groups randomly： normal controls for group I , Alzheimer＇s disease model for group Ⅱ ,hypercholesterolemia involved in Alzheimer＇s disease model for group m, and treatment by Sibraea angustata model for group IV. Then observed the general reaction of each group;The content of cholesterol in the blood and brain tissue was detected; The neurofibrillary tangles ,β amyloidal protein deposits and loss of midbrain neurons of hippocampus and cortex tissue were observed. In time fluorescence quantitative method was used to detect the hippocampus and cortex tissue metabolism of cholesterol key genes CYP46al and APOE expression. The tau expression was determined by Western-blot. Results：Compared with the normal group, group lI, Ⅱ turned to be listless,poor appetite, fur rough, especially group Ⅲ, group IV after the treatment of Sibraea angustata extract, the animals turned to be spirit better, increased appetite, fur smooth; Group U ＇ s cholesterol content did not differ significantly compared with the normal group. While Group Ⅲ was obviously higher than that of group Ⅱ （P 〈 0. 05 ）, and group Ⅳ was lower than those of all the others after the treatment of Sibraea angustata. Actually the content of cholesterol of group Ⅱ, Ⅲ increased obviously, especially grouplll ,while decreases in group Ⅳ after the treatment. Compared with group I ：the expression of APOE mRNA RMFI both increased in group Ⅱ ＆Ⅲ （ P 〈 0. 01 ）, and group Ⅲ was higher than group Ⅱ （ P 〈 0. 01 ）, but group IV decreased dramatically. The expression of CYP46al RMFI decreased of group Ⅱ ＆ Ⅲ （ P 〈 0.01 ）, while that of group IV increased; The expression of tan protein phosphorylation was down-regulated in group Ⅱ, Ⅲ, especially group Ⅲ, that of grouplV was down-regulated. Conclusion ：Hypercho

关 键 词：阿尔兹海默病 高胆固醇血症 柳茶提取物 

分 类 号：R285.5[医药卫生—中药学]