Sun Wen-Wen, Xie Bin-Fang, Liu Hui, Liu Xin
Department of Pathology and Pathophysiology, Basic Medical Science of Lanzhou University, Lanzhou 730000, China.
Zhong Yao Cai. 2012 Apr;35(4):596-602.
To observe the role of hypercholesterolemia in the outbreak of Alzheimer's disease (AD) and the treatment effect of Sibraea angustata extract.
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 III, 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, beta 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 CYP46a1 and APOE expression. The tau expression was determined by Western-blot.
Compared with the normal group, group II, III 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 II's cholesterol content did not differ significantly compared with the normal group. While Group II 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 group III, 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 tau protein phosphorylation was down-regulated in group II, III, especially group III, that of group IV was down-regulated.
Hypercholesterolemia can promote the happening of the AD. The extract of Sibraea angustata can not only reduce the content of cholesterol in the AD animal effectively but also improve brain tissue pathology. It is possible that adjusting the brain key enzyme cholesterol metabolism in gene or protein level may be one of the mechanisms.
观察高胆固醇血症在阿尔茨海默病（AD）发病中的作用及窄叶鲜卑花提取物的治疗效果。
将大鼠随机分为四组：Ⅰ组为正常对照组，Ⅱ组为阿尔茨海默病模型组，Ⅲ组为合并高胆固醇血症的阿尔茨海默病模型组，Ⅳ组为窄叶鲜卑花提取物治疗组。观察各组大鼠的一般反应；检测血液及脑组织中胆固醇含量；观察海马及皮质组织神经原纤维缠结、β淀粉样蛋白沉积及中脑神经元丢失情况。采用实时荧光定量法检测海马及皮质组织中胆固醇代谢关键基因CYP46a1和APOE的表达。采用Western - blot法检测tau蛋白表达。
与正常组相比，Ⅱ、Ⅲ组大鼠精神萎靡、食欲减退、皮毛粗糙，尤以Ⅲ组为甚，Ⅳ组经窄叶鲜卑花提取物治疗后，动物精神状态好转、食欲增加、皮毛顺滑；Ⅱ组胆固醇含量与正常组相比无显著差异。Ⅱ组明显高于Ⅰ组（P < 0.05），Ⅳ组经窄叶鲜卑花提取物治疗后低于其他各组。实际上，Ⅱ、Ⅲ组胆固醇含量明显升高，尤以Ⅲ组为甚，Ⅳ组治疗后降低。与Ⅰ组相比：Ⅱ、Ⅲ组APOE mRNA相对荧光定量值（RMFI）均升高（P < 0.01），且Ⅲ组高于Ⅱ组（P < 0.01），但Ⅳ组显著降低。Ⅱ、Ⅲ组CYP46al RMFI降低（P < 0.01），Ⅳ组升高；Ⅱ、Ⅲ组tau蛋白磷酸化表达下调，尤以Ⅲ组为甚，Ⅳ组也下调。
高胆固醇血症可促进AD的发生。窄叶鲜卑花提取物不仅能有效降低AD动物体内胆固醇含量，还能改善脑组织病理状态。在基因或蛋白水平调节脑内关键酶胆固醇代谢可能是其作用机制之一。
