【作者】 王凯；

【导师】 王健；

【作者基本信息】 长春中医药大学 ， 中医内科学（专业学位）， 2022， 博士

【摘要】 目的:通过分析脑卒中高危人群中医证候要素相关特征,以及利用脑血流自动调节功能变化评价天麻钩藤饮和涤痰汤的干预效果,为中医药防治脑卒中提供新的靶点和机制。方法:1.于2021年1月1日-2021年2月15日,收集脑卒中高危人群患者644例,对其证候要素、高血压、糖尿病等脑卒中相关危险因素、生活质量进行调查登记,并录入数据库。应用SPSS 25.0进行描述性分析、卡方检验、秩和检验等方法对中医药干预前后证候要素特征及其他临床因素进行相关性研究。2.基于利用中药系统药理学分析平台(TCMSP)、Pubchem(https://pubchem.ncbi.nlm.nih.gov/)、Swiss ADME(http://www.swissadme.ch/)、Genecard数据库(www.genecards.org/)等数据库平台,对天麻钩藤饮、涤痰汤进行复方活性成分、GO功能富集分析、KEGG通路富集分析,构建成分-靶点-通路网络图,分析其对脑血流自动调节功能潜在作用靶点和机制,并用Cytoscape3.9.0软件和R软件进行可视化处理。3.对2021年1月1日-2021年2月15日收集102例脑卒中高危人群患者(中药组56例、对照组46例),应用SPSS 25.0进行描述性分析、卡方检验、单因素及多元归回分析等方法分析其干预前后的中医证候积分变化特征及脑血流自动调节功能变化及影响因素。结果:1.本研究对644例脑卒中高危人群临床的特进行分析,结果表明女性数量大于男性,51-70岁是主要的分布年龄,受教育程度普遍在高中及以下。本研究的主要病例分布以东北地区为主,饮食偏咸和吃蔬菜是主要的饮食习惯,体重普遍偏重,腰臀比和BMI方面性别没有显著性差异。危险因素分布方面,缺乏体育活动、家族史和高血压分布较多。在只合并3种危险因素的人群种,以吸烟+缺少体育活动+家族史为主要分布特征。2.在中药组和对照组证候积分方面:整体上看中药组干预前后证候积分变化明显优于对照组。尽管在痰湿证和内火证对照组干预前证候积分小于中药组,但在干预后中药组的证候积分改善程度还是优于对照组。在瘀血证和阴虚证中两组干预前后证候积分均无显著性改变。通过3个时点的评价,中药组的内风证、内火证、气虚证、痰湿证证候积分改变持续降低,而对照组只对内风证的干预效果较为明显。同时经过多因素线性回归分析生活质量评分与内火证、气虚证、痰湿证存在呈负相关。两组生活质量评分显示中药组整体病例干预前生活质量评分低于对照组,而在干预后中药组的生活质量评分明显高于对照组,说明中药干预后脑卒中高危人群的生活质量得到显著改善。3.结果表明天麻钩藤饮和涤痰汤对于脑血管舒张功能有潜在作用。其可能通过调控血管舒张因子(前列环素、一氧化氮等)、血管收缩因子(血栓素A2、5羟色胺等)的表达、离子的交换、血管内皮细胞的增殖和凋亡、神经细胞的保护、抗炎、抗氧化等靶点,潜在的作用通路包括PI3K-Akt信号通路、MAPK信号通路、Ras信号通路等。因此天麻钩藤饮和涤痰汤改善脑血流自动调节功能具有一定可能性。4.本研究的结果表明在证候要素中,中药组证候积分干预前后对比内风证6.79±5.08下降为4.82±5.04、内火证22.38±11.81下降为17.88±10.88、痰湿证22.14±8.43下降为13.55±6.75、血瘀证3.77±5.59下降为2.98±5.27、气虚证22.21±16.55下降为15.71±9.3、阴虚证3.84±5.56下降为2.59±3.93,并且痰湿证、TIA、糖尿病史与相位差存在线性关系。结论:1、天麻钩藤饮和涤痰汤可以改善脑卒中高危人群的证候要素积分提高其生活质量,同时本研究明确了脑卒中高危人群的证候要素积分与其生活质量存在线性关系。2、本研究发现相位差与痰湿证存在线性关系,说明了中医药对于改善脑卒中高危人群脑血流自动调节功能有巨大潜力。更多还原

【Abstract】 Objective: By analyzing the relevant characteristics of TCM syndrome elements in high-risk groups of stroke,and using the changes of cerebral blood flow automatic regulation function to evaluate the intervention effect of traditional Chinese medicine,we can provide new targets and mechanisms for the prevention and treatment of stroke.Methods: 1.From January 1,2021 to February 15,2021,644 patients with high risk of stroke were collected,their syndrome elements,stroke related risk factors and quality of life were investigated,registered and entered into the database.SPSS 25.0was used for descriptive analysis,chi square test and rank sum test to study the correlation between the characteristics of syndrome elements and other clinical factors before and after TCM intervention.2.Based on the utilization of tcmsp and Pub Chem(https://pubchem.ncbi.nlm.nih.gov/)、Swiss ADME(http://www.swissadme.ch/),GENECARD database(www.genecards.Org /)and other database platforms,the compound active components,go function enrichment analysis and KEGG pathway enrichment analysis of Tianma Gouteng Decoction and Ditan Decoction were carried out,the component target pathway network diagram was constructed,and its potential target and mechanism on the cerebral autoregulation were analyzed with Cytoscape 39.0 software and R software for visual processing.2.Based on the utilization of tcmsp and Pub Chem(https://pubchem.ncbi.nlm.nih.gov/)、 Swiss ADME(http://www.swissadme.ch/),GENECARD database(www.genecards.Org /)and other database platforms,the compound active components,go function enrichment analysis and KEGG pathway enrichment analysis of Tianma Gouteng Decoction and Ditan Decoction were carried out,the component target pathway network diagram was constructed,and its potential target and mechanism on the cerebral autoregulation were analyzed with Cytoscape 3 9.0 software and R software for visual processing.3.From January 1,2021 to February 15,2021,102 patients with high risk of stroke(56 in traditional Chinese medicine group and 46 in control group)were collected.Descriptive analysis,chi square test,univariate and multivariate regression analysis were carried out by SPSS 25.0 to analyze the changes of TCM syndrome integral before and after intervention,the changes and influencing factors of cerebral blood flow automatic regulation function.Results: 1.This study analyzed the clinical characteristics of 644 high-risk groups of stroke.The results showed that the number of women was greater than that of men,51-70 years old was the main distribution age,and the education level was generally in high school and below.As the main cases in this study are mainly distributed in Northeast China,salty diet and eating vegetables are the main eating habits,weight is generally overweight,and there is no significant difference between sexes in waist hip ratio and BMI.In terms of the distribution of risk factors,lack of physical activity,family history and hypertension are more distributed.In the population with only three risk factors,smoking + lack of physical activity + family history are the main distribution characteristics.2.In the aspect of syndrome score of traditional Chinese medicine group and control group: on the whole,the change of syndrome score of traditional Chinese medicine group before and after intervention is significantly better than that of control group.Although the syndrome score in the control group of phlegm dampness syndrome and internal fire syndrome before intervention is less than that in the traditional Chinese medicine group,the improvement of syndrome score in the traditional Chinese medicine group is better than that in the control group after intervention.In blood stasis syndrome and yin deficiency syndrome,the syndrome scores of the two groups had no significant change before and after intervention.Through the evaluation of three time points,the integral changes of internal wind syndrome,internal fire syndrome,Qi deficiency syndrome and phlegm dampness syndrome in the traditional Chinese medicine group continued to decrease,while the intervention effect of the control group on internal wind syndrome was more obvious.At the same time,through multi factor linear regression analysis,the score of quality of life was negatively correlated with internal fire syndrome,Qi deficiency syndrome and phlegm dampness syndrome.The quality of life scores of the two groups showed that the overall quality of life score of the traditional Chinese medicine group was lower than that of the control group before the intervention,and the quality of life score of the traditional Chinese medicine group was significantly higher than that of the control group after the intervention,indicating that the quality of life of high-risk groups of stroke was significantly improved after the intervention of traditional Chinese medicine.3.The results show that maguoteng Decoction and Ditan Decoction have potential effects on cerebral vasodilation.It may regulate the expression of vasodilator factors(prostacyclin,nitric oxide,etc.),vasoconstrictor factors(thromboxane A2,serotonin,etc.),ion exchange,proliferation and apoptosis of vascular endothelial cells,protection of nerve cells,anti-inflammatory,antioxidant and other targets.The potential action pathways include PI3 K Akt signal pathway,MAPK signal pathway,RAS signal pathway and so on.Therefore,Tianma Gouteng Decoction and Ditan Decoction have a certain possibility to improve the automatic regulation function of cerebral blood flow.4.The results of this study showed that among the syndrome elements,the syndrome score of the traditional Chinese medicine group decreased from 6.79 ±5.08 to 4.82 ± 5.04,22.38 ± 11.81 to 17.88 ± 10.88,22.14 ± 8.43 to 13.55 ±6.75,3.77 ± 5.59 to 2.98 ± 5.27,22.21 ± 16.55 to 15.71 ± 9.3,3.84 ± 5.56 to2.59 ± 3.93,and the syndrome of phlegm dampness,TIA There is a linear relationship between the history of diabetes and the phase difference.Conclusion: 1.Tianma Gouteng Decoction and Ditan Decoction can improve the syndrome factor score of stroke high-risk groups and improve their quality of life.At the same time,this study made it clear that there is a linear relationship between the syndrome factor score of stroke high-risk groups and their quality of life.2.This study found that there is a linear relationship between phase difference and phlegm dampness syndrome,which shows that traditional Chinese medicine has great potential to improve the automatic regulation function of cerebral blood flow in high-risk groups of stroke.更多还原