摘要
目的评估加味地黄饮子治疗血管性痴呆(VD)的有效性及安全性,并利用全外显子测序探究其作用机制及VD易感基因。方法纳入陕西中医药大学第二附属医院住院及门诊VD患者75例,采用随机数字表法分为对照组(37例,常规西药)和试验组(38例,常规西药+加味地黄饮子),疗程3个月。比较2组一般资料、中医证候积分、简易精神状态检查量表(MMSE)评分、日常生活能力量表(ADL)评分、日常社会行为能力量表(Blessed)评分及不良反应。选取36例VD肾精亏虚证患者外周血进行全外显子测序,筛选易感基因,结合网络药理学分析加味地黄饮子靶点,构建“药物-基因”网络,富集分析关键通路。结果2组患者基线资料比较差异无统计学意义(P>0.05),具有可比性。与治疗前比较,2组治疗后MMSE评分显著升高,中医证候积分、ADL评分显著降低(P<0.05)。与对照组比较,试验组中医证候积分、MMSE评分、ADL评分及临床疗效显著优于对照组(P<0.05)。Blessed评分显示,试验组在改善患者生活能力及日常习惯方面更有优势(P<0.05)。2组患者治疗期间均未见不良反应。全外显子测序检出1250744个单核苷酸多态性(SNP)位点、37314个插入标记缺失(InDel)位点,经筛选得到3041个VD易感基因,发现参与对营养物质水平的反应、MAPK级联的正向调节、循环系统中的血管过程、营养物质反应等生物过程及富集于PI3K-Akt、胆碱能/谷氨酸能突触、脂质和动脉粥样硬化通路。加味地黄饮子共854个潜在靶点与易感基因取交集得353个共同靶点,取前10个关键基因分析发现,参与对胞嘧啶丝氨酸磷酸化的正调控作用、miRNA介导的基因沉默调控、细胞对氧水平降低的反应等生物学过程,富集于PI3K-Akt、脂质和动脉粥样硬化等信号通路。结论加味地黄饮子能改善VD患者症状、保护认知功能、提高日常生活能力,安全性良好。其机制可能通过PI3K-Akt信号通路及脂质动脉粥样硬化信号通路,调控易感基因,改善脂质代谢、炎症反应和氧化应激。
Objective To evaluate the efficacy and safety of Jiawei Dihuang Decoction in the treatment of vascular dementia(VD);To explore its mechanism and the VD susceptibility genesby using whole exome sequencing.Methods A total of 75 patients with VD who were hospitalized or received outpatient treatment at The Second Affiliated Hospital of Shaanxi University of Chinese Medicine were included.They were divided into the control group(37 cases,treated with conventional Western medicine)and the experimental group(38 cases,treated with conventional Western medicine+Jiawei Dihuang Decoction)using random number table method.The treatment course was 3 months.The general data,TCM syndrome scores,MMSE scores,ADL scores,Blessed scores and adverse reactions of the two groups were compared.Peripheral blood samples from 36 patients with kidney-yin deficiency type VD were selected for whole exome sequencing.Susceptible genes were screened,and the targets of Jiawei Dihuang Decoction were analyzed by network pharmacology.A“drug-gene”network was constructed,and key pathways were enriched.Results There was no statistical significance in the baseline data between the two groups(P>0.05),and they were comparable.Compared with before treatment,the MMSE scores of patients in both groups significantly increased after treatment,while TCM syndrome scores and ADL scores significantly decreased(P<0.05).Compared with the control group,the TCM syndrome scores,MMSE scores,ADL scores and clinical efficacy of the experimental group were significantly better than those of the control group(P<0.05).Moreover,the Blessed score showed that the experimental group had more advantages in improving the patients’living ability and daily habits(P<0.05).No adverse reactions were observed in both groups during the treatment period.A total of 1250744 single nucleotide polymorphism(SNP)loci and 37314 insertion and deletion(InDel)loci were detected by whole exome sequencing.After screening,3041 VD susceptibility genes were obtained.It was found that they were involved in biological processes such as the response to nutrient levels,positive regulation of the MAPK cascade,vascular processes in the circulatory system,the response to nutrients,etc.And enriched in PI3K-Akt,cholinergic/glutamatergic synapses,lipid metabolism and atherosclerosis pathways.The potential targets of 854 of Jiawei Dihuang Decoction were intersected with the susceptibility genes to obtain 353 common targets.The top 10 key genes were analyzed and found to be involved in positive regulation of cytosine-serine phosphorylation,miRNA mediated gene silencing regulation,and the response of cells to decreased oxygen levels,etc.They were enriched in PI3K-Akt,lipid and atherosclerosis signaling pathways.Conclusion Jiawei Dihuang Decoction can alleviate the symptoms of patients with VD,protect cognitive function,enhance their ability of daily living,and has good safety profile.Its mechanism may involve regulating susceptibility genes through PI3K-Akt signaling pathway and lipid atherosclerosis signaling pathway,and improving lipid metabolism,inflammatory response and oxidative stress.
作者
杨慧雯
杨娟娟
郝志强
陈亮亮
申艳方
卫培峰
缪峰
YANG Huiwen;YANG Juanjuan;HAO Zhiqiang;CHEN Liangliang;SHEN Yanfang;WEI Peifeng;MIAO Feng(Shaanxi University of Chinese Medicine,Xianyang 712046,China;The Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China)
出处
《中国中医药信息杂志》
2025年第10期134-141,共8页
Chinese Journal of Information on Traditional Chinese Medicine
基金
陕西省重点研发计划(2021ZDLS04-11)
陕西省“特支计划”人才项目(2021年)
咸阳市科学技术研究与发展计划(2021ZDYF-SF-0044)
“双链融合”中青年科研创新团队建设项目(2022-SLRH-YQ-008)
秦创原中医药产业创新聚集区项目(L-2024-QCY-ZYYJJQ-251)。
关键词
全外显子测序
加味地黄饮子
血管性痴呆
易感基因
临床研究
whole exome sequencing
Jiawei Dihuang Decoction
vascular dementia
susceptibility genes
clinical study
