机构地区:[1]湖北中医药大学老年医学研究所,武汉430065
出 处:《中国实验方剂学杂志》2017年第12期96-102,共7页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家自然科学基金重点项目(81130064);国家自然科学基金项目(81001542)
摘 要:目的:观察补肾化痰益智方(BSHT)对APPV717I转基因小鼠干预效果,揭示其可能作用机制。方法:将3月龄APPV717I转基因小鼠120只分为2批,每批60只,每批又随机分为5组,分别为多奈哌齐(0.000 92 g·kg^(-1)·d^(-1))组,补肾化痰益智方低、中、高剂量组(5.2,10.4,20.8 g·kg^(-1)·d^(-1)),模型组(APP),每组12只(雌雄各半);同月龄遗传背景相同的C57BL/6J小鼠24只作为正常组,灌胃给药,模型组及正常组予等容积双蒸水灌胃,每日1次。第1批小鼠给药8个月,第2批给药4个月,最后同时以Morris水迷宫进行行为学检测,分别以酶联免疫吸附测定(ELISA)和免疫印迹法测定(Western blot)海马神经元Tau蛋白磷酸化(p-Ser 199/202,Tau-1)的表达水平。结果:行为学实验结果表明,与正常组比较,模型组小鼠的潜伏期有所延长(P<0.05,P<0.01);各治疗组与模型组比潜伏期明显缩短(P<0.05)。ELISA和Western blot实验结果表明,与正常组比较,模型组小鼠海马神经元的Ser199/202磷酸化位点磷酸化程度显著升高(P<0.01);各治疗组Ser199/202磷酸化位点磷酸化水平较模型组比明显缩短(P<0.05,P<0.01)。结论:补肾化痰益智方可以改善Ser199/202磷酸化位点磷酸化程度,防止神经原纤维缠结(NFT)的形成,从而改善APPV717I转基因小鼠早期的学习记忆能力。Objective: To investigate the intervention effect of Bushen Huatan Yizhi decoction (BSHT) in APPV717I transgenic mice and explore its possible mechanism. Method: The 120 three months old APPV717I transgenic mice were randomly divided into two batches, n = 60 in each batch. The mice in each batch were randomly divided into model group ( APP), Donepezil group (0. 000 92 g·kg^- 1·d^- 1 ), BSHT low dose group (5.2 g·kg^- 1·d^- 1), middle dose group (10.4 g·kg^- 1·d^- 1), and high dose group (20.8 g·kg^- 1·d^- 1), n = 12 in each group (6 males and 6 females). Another 24 C57BL/6J mice of the same age were set as a normal group, and the mice in model group and normal group received intragastric administration of equivalent volume of distilled water, 1 time/day. The first batch of mice received drug administration for 8 months, and the second batch for 4 months. Behavioral ability was measured in Morris water maze finally, and the expression levels of Tau protein hosphorylation (p-Ser 199/202, Tau-1 ) in the hippocampus was determined by using enzyme linked immunosorbent assay (ELISA) and Western blot. Result : Behavioral experiment results showed that, as compared with the normal group, the latency was prolonged in model group mice (P 〈 0.05, P 〈 0.01 ). After months treatment, the latency was shortened in various treatment groups as compared with model group (P 〈 0.05 ). ELISA and Western blot assay showed that as compared with the normal group, the phosphorylation degree of Ser199/202 phosphorylation sites in hippocampal neurons was increased significantly in model group (P 〈 0.01 ) ; and the phosphorylation degree of Ser199/202 phosphorylation sites in various treatment groups was significantly lower than that in model group (P 〈0.05, P 〈0. 01 ). Conclusion: Bushen Huatan Yizhi decoction can improve the phosphorylation degree of Ser199/202 phosphorylation sites, prevent neurofibrillary tangle (NFT) formation, and thus improve the earl
关 键 词:补肾化痰益智方 老年性痴呆 APPV717I转基因小鼠 MORRIS水迷宫 学习记忆能力 神经原纤维缠结 TAU蛋白磷酸化
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...
正在载入数据...