目的:探求地黄饮子对AD模型大鼠脑内Aβ生成的干预机制。方法:清洁级健康雄性Wistar大鼠100只,随机取10只为空白组,其余90只随机平均分为6组:假手术组,模型组,西药组,中药高、中、低剂量组,每组15只。各组腹腔注射D-gal 4周,西药组给予盐酸多奈哌齐,中药高、中、低剂量组给予高、中、低剂量地黄饮子,模型组、假手术组给予等量0.9%氯化钠溶液灌胃。4周后,药物干预组大鼠在海马坐标区注射Aβ_(1-40),假手术组大鼠在上述部位注射0.9%氯化钠溶液。1周后HE染色和免疫组化法观察脑组织中β-淀粉样蛋白相关因子水平。结果:各组模型大鼠β-APP、BACE及Aβ免疫组化染色示,模型组表达显著升高(P〈0.01);与模型组相比中药各剂量组均可显著下调β-APP、BACE及Aβ的表达(P〈0.01);各药物组间比较以中药高剂量组为优。结论:地黄饮子能够抑制β-APP经由淀粉样肽源性途径的裂解过程,使Aβ在脑组织中的表达水平降低。
Objective: To explore the intervention mechanism of Dihuang Drink on generation of Aβ in the brain of AD model rats. Methods: 100 clean grade healthy male Wistar rats were randomly divided into 7 groups: normal control group(n=10), sham operation group(n=15), model group(n=15), western medicine control group(n=15), Dihuang Drink high, middle and low dose groups(n=15). The AD model was established by intraperitoneal injection with D-gal for 4 weeks. At the same time, the western medicine control group was given donepezil hydrochloride, high, middle and low dose of Dihuang Drink groups were given Dihuang Drink in corresponding dose, the model group and sham operation group were given equal volume of normal saline by gavage. After 4 weeks, drug intervention groups were injected Aβ_(1-40) in the hippocampus of coordinate district, sham operation group was injected normal saline in the same position. A week later, HE staining and immunohistochemistry were used to observe the levels of beta amyloid related protein in brain tissue. Results: Compared to model group, Dihuang Drink could down-regulate β-APP, BACE and Aβ levels in brain of AD model rats(P〈0.01), and improve the morphology of neurons in hippocampus(P〈0.01). Conclusion: Dihuang Drink could inhibit β-APP expression level through the cleavage of amyloid peptide derived pathway, and decrease the Aβ expression level in the brain tissue.