活忆饮对阿尔茨海默病模型大鼠β-淀粉样肽1-40和烟碱型胆碱受体的影响

Effects of Huoyi decoction(活忆饮) on expressions of amyloid-βpeptide1-40 and neuronal nicotinic acetylcholine receptor in different brain sections of rat′s model with Alzheimer′s disease

目的:观察中药方剂活忆饮对实验性阿尔茨海默病(AD)模型大鼠脑内不同部位β-淀粉样肽1-40(Aβ1-40)和烟碱型胆碱受体(nAchR)表达的影响,探讨中医药治疗AD的方法。方法:成年健康雌性Wistar大鼠15只,在脑立体定位仪上切断大鼠双侧穹窿-海马伞,切除双侧卵巢,建立实验性AD动物模型。按随机数字表法分为3组,每组5只。1AD组:4.8 ml生理盐水灌胃,每日1次;2雌激素治疗组(E2组):苯甲酸雌二醇(1 mg/kg)皮下注射,每周1次;3活忆饮治疗组:中药方剂活忆饮每次灌胃4.8 ml,每日1次(活忆饮主要由补肾益精中药熟地,活血行气中药黄芪,以及泻火解毒中药黄连等组成,水煎浓缩至含生药量1 kg/L汤剂)。所有大鼠均治疗28 d。采用免疫组化染色观察大脑皮质区、海马CA1区、杏仁复合体区、Meynert核区的Aβ1-40、nAchR阳性细胞表达。结果:活忆饮治疗组和E2组皮质区、海马CA1区、杏仁复合体区、Meynert核区nAchR阳性细胞数均显著高于AD组,而Aβ1-40阳性细胞数显著低于AD组(P<0.05或P<0.01)。活忆饮治疗组大脑皮质区、杏仁复合体区nAchR阳性细胞数较E2组均明显升高,海马CA1区和Meynert核区Aβ1-40阳性细胞数则均较E2组显著降低(P<0.05或P<0.01)。结论:中药方剂活忆饮可以提高AD模型大鼠脑内不同部位nAchR表达,降低Aβ1-40表达,具有干预AD病理过程的作用。

Objective： To observe the effect of Chinese traditional herbals Huoyi decoction（活忆饮） on expressions of amyloidβ-peptide1-40（Aβ140） and neuronal nicotinic acetylcholine receptor（nAchR） in different sections of rat＇s model with Alzheimer＇s disease（AD） and approach the method of traditional Chinese medcine for treatment of AD disease.Methods： The rat＇s model of AD was made by excision of bilateral fimbria-fornix of hippocampus in the brain under a stereotaxic apparatus,and the bilateral ovariectomy.Fifteen healthy female Wistar rats were randomly divided into three groups（each n=5）： ①AD group： 4.8 ml normal saline was infused into the stomach once a day;②estradiol supplement therapy group（E2 group）： estradiol（1 mg/kg） subcutaneouly injection,once a week;③Huoyi decoction group： 4.8 ml Huoyi decoction was administered into the stomach,once a day（The Huoyi decoction was composed of traditional Chinese herbals of prepared rehmannia root for nourishing the kidney and strengthening the essence（补肾益精）,astragalus root for promoting blood and qi circulation（活血行气）,and gold-thread root（Rhizoma Coptidis for purging intense heat and removing toxic substances（泻火解毒）;the above water decoction was concentrated to 1 L containing 1 kg crude drug（1 kg/L））.The changes of expression of the Aβ1-40 and nAchR positive cells were observed in the hippocampus CA1,cerebral cortex,amygdala,Meynert nucleus with immunohistochemical method.All the rats were observed and treated for 28 days.Results： The nAchR positive cells were increased and Aβ1-40 positive cells were decreased distinctly in the Huoyi decoction group and E2 group in comparisons with those in the AD group in the hippocampus CA1,cerebral cortex,amygdala and Meynert nucleus（P〈0.05 or P〈0.01）.In the cerebral cortex and amygdala,the nAchR positive cells in Huoyi decoction group were increased more significantly than that in E2 group （P〈0.05 or P〈0.01）,while in the hippocampus CA1 and Meynert nucleus,the Aβ1-40 positive cells in Huoyi decoction group were more decreased markedly than that in E2 group（P〈0.05 or P〈0.01）.Conclusion： The traditional Chinese herbals Huoyi decoction can elevate the expression of nAchR and decrease the expression of Aβ1-40 in many brain sections of rat＇s model with AD,and has the action of interference in the pathological process of AD.