涤痰汤及其拆方对阿尔茨海默病大鼠神经保护作用的研究

Neuroprotection of Ditan Decoction and Its Decomposed Recipes on Alzheimer′s Disease Rats

目的观察涤痰汤及其拆方对阿尔茨海默病(Alzheimer′s disease,AD)模型大鼠的神经保护作用。方法通过对SD大鼠海马注射Aβ1-42复制AD大鼠模型。84只动物随机分为对照组、模型组、涤痰汤全方组、涤痰汤拆方1组(半夏+姜南星)、涤痰汤拆方2组(橘红+石菖蒲)、涤痰汤拆方3组(人参+茯苓+甘草)、涤痰汤拆方4组(枳实+竹茹),每组12只。灌胃4周后利用Morris水迷宫、Bielschowsky′s银染、Western Blot、ELISA分别检测各组大鼠空间学习记忆能力、海马神经原纤维缠结情况、β淀粉样前体蛋白(APP)磷酸化水平和β-淀粉样蛋白(Aβ)含量的变化。结果与对照组比较,模型组大鼠空间学习记忆能力明显下降(P<0.05,P<0.01),神经原纤维缠结明显增多(P<0.01),APP蛋白Thr668位点的磷酸化水平明显增加(P<0.01),海马Aβ1-42的生成明显增加(P<0.01)。与模型组比较,涤痰汤全方组及各拆方组模型鼠空间学习记忆障碍均改善(P<0.05,P<0.01),模型鼠海马的神经原纤维缠结减轻,APP蛋白Thr668位点的磷酸化水平下调(P<0.05,P<0.01),海马Aβ1-42的生成减少(P<0.01)。结论涤痰汤全方组和拆方组能减轻AD模型鼠脑神经病理学改变、减少Aβ的生成,从而发挥神经保护作用。

Objective To observe the neuroprotective effects of Ditan Decoction(DTD)and its decomposed recipes on Alzheimer′s disease(AD)model rats.Methods AD rat model was duplicated by injecting Aβ1-42 into bilateral hippocampus of Sprague Dawley rats.The rats were treated with DTD and each decomposed recipe by gastrogavage.Totally 84 rats were randomly divided into the control group,the model group,DTD group,DTD1 group 1(Pinellia Ternata+Rhizoma Arisaematis),DTD2 group(Exocarpium Citri Rubrum+Acorus Tatarinowii),and DTD3 group(Ginseng+poria+licorice),DTD4 group(immature bitter orange+bamboo shavings),12 in each group.Morris water maze,Bielschowsky′s silver staining,Western Blot,and ELISA were used to detect the spatial learning and memory abilities,the changes of neurofibrillary tangles,β-amyloid precursor protein(APP)phosphorylation levels,andβ-amyloid(Aβ)levels in each group after 4 weeks gastric administration.Results Compared with the control group,the spatial learning and memory abilities of the model group were significantly decreased(P<0.05,P<0.01),the neurofibrillary tangles were significantly increased(P<0.01),the phosphorylation of APP protein at Thr668 was significantly increased(P<0.01),and the production of hippocampal Aβ1-42 were significantly increased(P<0.01).Compared with the model group,the spatial learning and memory impairment of model rats were alleviated(P<0.05,P<0.01),the neurofibrillary tangles in the hippocampus were attenuated,the phosphorylation level of APP at Thr668 were down-regulated(P<0.05,P<0.01),and the production of Aβ1-42 were reduced(P<0.01)in all DTD groups.Conclusion Neuropathological changes were attenuated and the production of Aβ1-42 reduced in AD model rats by all TDT groups,thus exerting neuroprotective effects.