阿尔茨海默病“肾虚酿毒伤髓”病机演变模型构建及其应用  

Construction and Application of Model for Pathogenesis Evolution of Alzheimer′s Disease:“Kidney Deficiency Breeds Toxicity and Injures Marrow”

作　　者：钱小溪 陆韵薇[1] 吴同越 于顾然[1] QIAN Xiaoxi;LU Yunwei;WU Tongyue;YU Guran(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu,China)

机构地区：[1]南京中医药大学附属医院,江苏南京210029

出　　处：《辽宁中医杂志》2024年第7期193-196,I0004,共5页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81573771);江苏省自然科学基金项目(BK20191506);江苏高校优势学科建设工程资助项目;江苏省研究生实践创新计划项目(SJCX22_0715)。

摘　　要：目的 根据肾-骨髓-血细胞-脑髓相互影响的中西医理论,建立一种阿尔茨海默病(Alzheimer′s disease, AD)“肾虚酿毒伤髓”模型,筛查AD有效中药,并初步探讨该模型的临床应用。方法 由于AD患者B淋巴细胞可以促进神经细胞产生Aβ毒素。将肾虚型AD患者外周血提取B淋巴细胞永生化,建立淋巴母细胞系(lymphoblastoid cell lines, LCL),并与人神经上皮瘤细胞(SKNMC)共培养,产生Aβ毒素,制成阿尔茨海默病“肾虚酿毒伤髓”模型。通过免疫荧光法检测Aβ_(1-42)的表达量,筛查有抑制Aβ_(1-42)生成的中药。并初步探讨该模型的临床应用。结果 与正常对照组相比,肾虚型AD模型中神经细胞Aβ_(1-42)的生成明显增多,具有统计学意义(P<0.01)。与肾虚模型组相比,白术、人参、黄芪、生地黄、梓醇减少了神经细胞Aβ_(1-42)的生成,差异具有统计学意义(P<0.01)。结论 白术、人参、黄芪、生地黄、梓醇可以减少AD中Aβ_(1-42)的生成。该模型除了筛查有效中药外,可以作为AD患者“肾虚酿毒”严重程度的生物标记物,及评价中药干预的疗效指标。Objective In this study,it established a model of Alzheimer′s disease(AD)based on traditional Chinese and Western medical theory of kidney-bone marrow-blood cell-brain marrow interaction,to screen the effective traditional Chinese medicines for AD and explore the clinical application of this model.Methods Since B lymphocytes in AD patients can promote the production of Aβtoxin by neuronal cells,the peripheral lymphocytes of AD patients were used to screen the effective herbal medicines for AD.B lymphocytes from peripheral blood of AD patients were immortalized to establish lymphoblastoid cell lines(LCL),and co-cultured with human neuroepithelioma cells(SKNMC)to produce Aβto make a model of AD.The expression of Aβ_(1-42) was detected by immunofluorescence assay,and Chinese herbal medicines that inhibited the production of Aβ_(1-42) were screened.The clinical application of the model was also initially explored.Results Compared with that in the normal control group,the production of Aβ_(1-42) in neuronal cells was significantly increased in the kidney deficiency AD model,which was statistically significant(P<0.01).Compared with the kidney deficiency model group,Baizhu(Atractylodis Macrocephalae Rhizoma),Renshen(Ginseng Radix Et Rhizoma),Huangqi(Astragali Radix),Shengdihuang(Rehmanniae Radix)and catalpol reduced the production of neuronal cell Aβ_(1-42),with statistically significant differences(P<0.01).Conclusion Baizhu(Atractylodis Macrocephalae Rhizoma),Renshen(Ginseng Radix Et Rhizoma),Huangqi(Astragali Radix),Shengdihuang(Rehmanniae Radix)and catalpol can reduce the production of Aβ_(1-42) in AD.This model can be used as a biomarker of the severity of“kidney deficiency breeding toxicity and injuring marrow”in AD patients and as an indicator of the efficacy of herbal interventions,in addition to screening the effective herbal medicines.

关 键 词：阿尔茨海默病 肾虚酿毒伤髓 B淋巴细胞 体外模型 

分 类 号：R277[医药卫生—中医学]