六味地黄丸和通络救脑滴丸对2种痴呆模型小鼠脑组织Aβ降解的影响

Effects of Liuwei Dihuang Pills and Tongluo Jiunao Dropping Pills on β-Amyloid Degradation in the Brain Tissue of Two Mouse Models of Dementia

目的:分析六味地黄丸和通络救脑滴丸对“肾精不足”和“毒损脑络”2种不同痴呆症模型动物脑组织Aβ降解的影响。方法:通过SAMP8小鼠和在SAMR1小鼠双侧海马区注射Aβ_(1-40)分别复制痴呆动物模型,采用水迷宫测定行为功能学,免疫组织化学染色(IHC)法检测海马和皮层中Aβ的表达,Western Blotting法检测海马和皮层中胰岛素降解酶(IDE)、低密度脂蛋白相关蛋白1(LRP1)和晚期糖基化终末产物受体(RAGE)蛋白的表达。结果:2种痴呆模型在游速、避暗错误次数、错误区时间、脑组织海马和皮层中IDE、RAGE和海马中LRP1等蛋白的表达,差异均有统计学意义(均P<0.05);与双侧海马区注射Aβ_(1-40)模型小鼠比较,SAMP8模型小鼠的游速和避暗错误次数下降,脑组织中RAGE表达升高,IDE和LRP1表达降低;通络救脑滴丸对改善双侧海马注射Aβ_(1-40)模型小鼠的避暗潜伏期、脑组织海马区IDE和RAGE的表达水平作用明显;六味地黄丸对改善SAMP8模型小鼠水迷宫寻台成功率、避暗潜伏期、脑组织皮层和海马区IDE表达和海马Aβ的表达水平作用明显。结论:六味地黄丸可改善“肾精不足”证痴呆模型小鼠脑组织Aβ清除障碍,通络救脑滴丸可改善“毒损脑络”证痴呆模型小鼠脑组织Aβ清除障碍。

Objective:To analyze the effects of Liuwei Dihuang Pills and Tongluo Jiunao Dropping Pills on the degradation ofβ-amyloid(Aβ)in the brain tissue of two mouse models of dementia with the syndromes of kidney essence insufficiency and toxin injuring brain collaterals,respectively.Methods:The two mouse models of dementia,SAMP8 mice and the SAMR1 mice injected with Aβ_(1-40) in the bilateral hippocampus areas,were used in this study.Morris water maze test was carried out to examine the behavioral differences of the two models.Immunohistochemistry was employed to examine the expression of Aβin the hippocampus and cortex.Western blotting was employed to determine the protein levels of insulin-degrading enzyme(IDE),low-density lipoprotein receptor-related protein 1(LRP1),and receptor for advanced glycation endproducts(RAGE)in the hippocampus and cortex.Results:The two dementia models showed differences in swimming speed,number of errors in passive avoidance,time in error zone,the protein levels of IDE and RAGE in the hippocampus and cortex,and the protein level of LRP1 in the hippocampus(P<0.05).Compared with model established by injection with Aβ_(1-40) in bilateral hippocampus areas,the SAMP8 mice showed reduced swimming speed and number of errors in passive avoidance,up-regulated protein level of RAGE and down-regulated protein levels of IDE and LRP1 in the brain tissue.Tongluo Jiunao Dropping Pills showed efficacy in terms of passive avoidance latency and the protein levels of IDE and RAGE in the hippocampus of the mice injected with Aβ_(1-40) in the hippocampus.Liuwei Dihuang Pills demonstrated efficacy in terms of the success rate of seeking platform,passive avoidance latency,the protein levels of IDE in the cortex and hippocampus,and the expression of Aβin the hippocampus in SAMP8 mice.Conclusion:Liuwei Dihuang Pills and Tongluo Jiunao Dropping Pills can mitigate the impaired Aβclearance in the mouse models dementia with the syndromes of kidney essence insufficiency and toxin injuring brain collaterals,respectively.