基于均匀设计的坎离颗粒改善肾性高血压病主效应中药筛选与验证  

Escreening and Verifying the Effective Ingredients of Kanli Granule on Renal Hypertension Based on Uniform Design Experimentation

作　　者：鲁成[1,2] 宋磊[1,3] 蒋梅先[1] 刘永明[1] LU Cheng;SONG Lei;JIANG Mei-xian;LIU Yongming(Cardiovascular Department of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,201203;Cardiovascular Department of Shanghai Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,200137;Cardiovascular Department of Traditional Chinese Hospital of Luan,Anhui,237000)

机构地区：[1]上海中医药大学附属曙光医院心血管科,上海201203 [2]上海中医药大学附属第七人民医院心血管科,上海200137 [3]六安市中医院心血管科,安徽237000

出　　处：《中国中西医结合杂志》2022年第6期711-715,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.81973611,No.81102671);全国西医学习中医优秀人才培养项目;上海市青年科技英才扬帆计划资助(No.20YF1436800);上海市第七人民医院人才培养(No.XX2018-03)。

摘　　要：目的筛选坎离颗粒中治疗肾性高血压病主效应中药,并验证其对肾性高血压病的疗效。方法采用腹主动脉缩窄诱导肾性高血压病大鼠模型,运用DPSVT.05版数据处理系统产生U20(2010)表,采用拟水平法确定均匀设计实验方案对坎离颗粒进行10因子(10味中药)10水平(10种剂量)20次实验,将100只雄性Wistar大鼠随机分为20组,每组5只。以干预后16周大鼠左前肢血压为筛选指标,根据均匀设计法进行逐步回归分析,筛选出主效应中药,并得到中药复方(简称筛选方)。验证实验,将50只雄性Wistar大鼠随机分为假手术组(蒸馏水10 mL/kg)、模型组(蒸馏水10 mL/kg)、筛选方组(筛选方混悬液1.125 g/mL)、坎离颗粒组(坎离颗粒混悬液0.675 g/mL)、缬沙坦组(缬沙坦混悬液0.72 g/L),每组10只。造模后8周开始干预,干预时间均为16周。测量造模后及干预4、12、16周大鼠左前肢血压,测量干预后各组大鼠肾脏重量及肾功能指标。结果坎离颗粒中黄芪、莪术、附子、葶苈子、茯苓组合且生药剂量分别为0.90、0.45、1.80、5.40、2.70 g/kg时,降低血压疗效最佳。验证实验结果显示,与假手术组比较,模型组各时间点收缩压升高(P<0.01),干预16周后血清肌酐(SCr)升高(P<0.01)、左肾重量/右肾重量(LK/RK)降低(P<0.01)。与模型组比较,各干预组干预后各时间点收缩压下降(P<0.01),干预16周后筛选方组、坎离颗粒组LK/RK升高(P<0.05),SCr下降(P<0.05)。结论黄芪、莪术、附子、葶苈子、茯苓是坎离颗粒改善肾性高血压病的主效应中药;应用均匀设计可以有效揭示复方疗效的物质基础。Objective To screen the main-effect Chinese medicine of Kanli Granule for treating renal hypertension,and to verify its curative effect on renal hypertension.Methods Rat model of renal hypertension was induced by abdominal aorta constriction,DPSVT.05 version data processing system was used to generate U20(2010)table,20 experiments with 10 factors(10 herbs)and 10 levels(10 kinds of dose)for Kanli Granules(using the pseudo-level method to determine the uniform design experiment plan)were conducted.One hundred rats were randomly divided into 20 groups with 5 rats in each group.Blood pressure of the left forelimb at 16 weeks after treatment was taken as the screening index,a stepwise regression analysis was carried out according to the uniform design method to screen out the main-effect Chinese medicine and obtain the Chinese medicine compound(screening formula).In the verification experiment,another 50 rats were randomly divided into sham operation group(distilled water 10 mL/kg),model group(distilled water 10 mL/kg),screening formula group(screening formula suspension 1.125 g/mL),Kanli Granule group(Kanli Granule suspension 0.675 g/mL),valsartan group(valsartan suspension 0.72 g/L),10 rats in each group.Intervention was started 8 weeks after modeling,and the intervention duration was 16 weeks.The blood pressure of the left forelimb after modeling,intervention 4,12 and 16 weeks was measured,and the renal function and kidney weights were measured after treatment.Results The Astragalus mongholicus Bunge,Curcuma phaeocaulis Valeton,Aconitum carmichaeli Debx,Lepidium apetalum Willd,and Poria cocos(Schw.)Wolf in Kanli Granules had the best effect when the crude drug dosages were 0.90,0.45,1.80,5.40,and 2.70 g/kg.The results of the verification experiment showed that compared with the sham operation group,the systolic blood pressure of the model group increased at each time(P<0.01),at intervention 16 weeks,the serum creatinine(SCr)increased,and the weight of left kidney/right kidney(LK/RK)decreased(P<0.05)in model group.C

关 键 词：坎离颗粒 均匀设计 肾性高血压病 腹主动脉缩窄 

分 类 号：R285.5[医药卫生—中药学]