基于均匀试验设计的黄芪-当归主要化学成分剂量配伍对血管平滑肌细胞增殖的影响  

Effect of Dose Compatibility of Main Chemical Components from Astragali Radix-Angelicae Sinensis Radix on Proliferation of VSMCs Based on Uniform Design

作　　者：陈凌波[1] 任芮彬 阎卉芳 邓常清[1] CHEN Lingbo;REN Ruibin;YAN Huifang;DENG Changqing(College of Integrated Traditional Chinese and Western Medicine,Medical School,Hunan University of Chinese Medicine,Changsha 410208,China;School of Mathematics,Southwest Jiaotong University,Chengdu 611756,China)

机构地区：[1]湖南中医药大学中西医结合学院医学院,长沙410208 [2]西南交通大学数学学院,成都611756

出　　处：《中国实验方剂学杂志》2023年第3期143-151,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81874406);湖南中医药大学中西医结合一流学科开放基金项目(2018ZXYJH02)。

摘　　要：目的:采用均匀试验设计方法,构建黄芪-当归中6种主要成分配伍抗血管平滑肌细胞(VSMCs)增殖的函数模型,分析这6种成分配伍与抑制VSMCs增殖的相关性,探讨黄芪-当归主要化学成分配伍对VSMCs增殖的影响、均匀设计试验在中药多成分配伍研究中的可行性。方法:采用细胞增殖及活性检测试剂盒(CCK-8)法测定黄芪-当归中6种成分配伍对血小板衍生生长因子-BB(PDGF-BB)诱导的大鼠VSMCs增殖的抑制作用,求得各成分半数抑制浓度(IC_(50))后,以芒柄花素、黄芪皂苷Ⅰ、黄芪甲苷、毛蕊异黄酮、阿魏酸、毛蕊异黄酮苷6种成分分别为自变量X_(1)、X_(2)、X_(3)、X_(4)、X_(5)、X_(6),细胞增殖抑制率为因变量Y,选用U_(24)^(*)(24^(9))均匀设计表和线性、二次多项式2种数学模型,以逐步回归方法筛选变量,得出理论上拟合较好的方程式。通过设定不同剂量的6种成分配伍进行验证试验,筛选出实际较优的关系方程式,并根据实验目的对筛选出的回归方程进行数据中心化处理,比较方程的各回归系数,以分析药物与药效的相关性。结果:黄芪-当归中6种成分均能抑制VSMCs增殖,且呈浓度依赖性。芒柄花素、黄芪皂苷Ⅰ、黄芪甲苷、毛蕊异黄酮、阿魏酸、毛蕊异黄酮苷的IC_(50)分别为123.453、113.184、81.655、141.159、101.187、151.016 mg·L^(-1)。经验证试验筛选出2个较优的数学模型,方程1和方程2分别为Y_(1)=73.137897-0.207888X_(1)+0.000508X_(2)^(2)+0.000347X_(1)X_(6)、Y_(2)=70.038433-0.236665X_(1)+0.000577X_(2)^(2)+0.000260X_(1)X_(4)+0.000415X_(1)X_(6)+0.000370X_(3)X_(5)。方程2经数据中心化处理后为Y=-1.480260-0.146281X_(1)+0.000673X_(2)^(2)+0.000314X_(1)X_(4)+0.000456X_(1)X_(6)+0.000737X_(3)X_(5),回归系数表明黄芪皂苷Ⅰ对细胞增殖抑制率起正向作用,芒柄花素与毛蕊异黄酮、芒柄花素与毛蕊异黄酮苷、黄芪甲苷与阿魏酸是以交互作用形式对细胞增殖发挥抑制效�Objective:The functional model of six major components of Astragali Radix-Angelicae Sinensis Radix combination against the proliferation of vascular smooth muscle cells(VSMCs)was constructed by uniform design,the relationship between the compatibility of these six main components and the inhibition of VSMCs proliferation was analyzed,and the effect of the compatibility of these main components of Astragali Radix-Angelicae Sinensis Radix on the proliferation of VSMCs as well as the feasibility of uniform design test in the study of multi-component compatibility of Chinese medicines were discussed.Method:Cell proliferation and toxicity assay kit(CCK-8)method was used to determine the inhibitory effect of the six components of Astragali Radix-Angelicae Sinensis Radix on platelet derived growth factor-BB(PDGF-BB)-induced VSMCs proliferation in rats and the half inhibitory concentration(IC_(50))of each component were obtained.Six chemical components of Astragali Radix-Angelicae Sinensis Radix(formononetin,astragaloside,astragalosideⅣ,calycosin,ferulic acid and calycosin-7-O-β-D-glucoside)were taken as the independent variables X_(1),X_(2),X_(3),X_(4),X_(5),X_(6),respectively,and the cell proliferation inhibition rate as the dependent variable Y.U_(24)^(*)(24^(9))uniform design table and mathematical models(including linear and quadratic polynomial)were selected,the stepwise regression method was used to screen the variables,and the better equations were obtained in theory.The actually better relationship equations were screened by setting the different dose compatibility of these six components for verification tests.According to the purpose of the experiment,the selected regression equation was processed by data centralization,so as to compare the regression coefficients of the data centralization equation and analyze the correlation between components and efficacy.Result:The six components of Astragali Radix-Angelicae Sinensis Radix could inhibit abnormal proliferation of VSMCs in a dose-dependent manner.IC50valu

关 键 词：均匀设计 回归分析 二次多项式 黄芪 当归 化学成分 半数抑制浓度(IC50) 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学] R289[理学—概率论与数理统计] O213[理学—数学]