注射用益气复脉(冻干)对心力衰竭合并高血压大鼠的药效及代谢组学研究  

Pharmacodynamics and metabolomics study of Yiqi Fumai Lyophilized Injection on rats with heart failure and hypertension

作　　者：杜韩 原景 魏栋 万梅绪[2,3] 张燕欣 李智 宋美珍 李德坤[2,3] 鞠爱春 叶正良[4] DU Han;YUAN Jing;WEI Dong;WAN Meixu;ZHANG Yanxin;LI Zhi;SONG Meizhen;LI Dekun;JU Aichun;YE Zhengliang(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Tasly Pride Pharmaceutical Co.,Ltd.,Tianjin 300410,China;Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections,Tianjin 300410,China;Tasly Pharmaceutical Co.,Ltd.,Tianjin 300402,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津天士力之骄药业有限公司,天津300410 [3]天津市中药注射剂安全性评价企业重点实验室,天津300410 [4]天士力医药集团股份有限公司,天津300402

出　　处：《药物评价研究》2023年第8期1629-1637,共9页Drug Evaluation Research

摘　　要：目的探讨注射用益气复脉(冻干)(YQFM)对心力衰竭合并高血压大鼠的药效作用及可能的代谢通路。方法构建结扎腹主动脉及肾动脉导致的心衰合并高血压大鼠模型,根据血压值随机分为模型组和YQFM组;假手术组进行同样操作但不结扎。每天尾iv给药1次,连续给药14 d。给药前后采用八通道无创血压仪检测大鼠血压;采用超声诊断仪检测大鼠心功能;采用ELISA法检测给药后大鼠血清心衰相关生化指标肌酸激酶同工酶(CK-MB)、心肌特异性肌钙蛋白T(cTnT)、脑钠肽(BNP)、氨基端前心钠肽(NT-proANP)和乳酸脱氢酶(LDH),血压相关生化指标肾素(Renin)、血管紧张素Ⅱ(AngⅡ)、血管紧张素转化酶1(ACE1)、血管紧张素原(aGT)水平;采用液相色谱质谱联用(LC-MS)法分析大鼠血清差异代谢物,将筛选出的差异性代谢物进行代谢通路富集分析。结果与假手术组相比,模型组大鼠左室射血分数(LVEF)、左室短轴缩短率(LVFS)显著降低(P<0.001),收缩压(SBP)显著升高(P<0.001),NT-proANP、BNP、CK-MB、cTnT、LDH、Renin、aGT、ACE1和AngⅡ水平均显著升高(P<0.001);与模型组相比,YQFM组的LVEF、LVFS均显著升高(P<0.001),SBP显著降低(P<0.001),血清NT-proANP、BNP、CK-MB、cTnT、LDH、Renin、aGT、ACE1和AngⅡ水平显著降低(P<0.001)。YQFM可能的作用通路为戊糖、葡萄糖醛酸转换,醚脂代谢,甘油磷脂代谢,嘌呤代谢及色氨酸代谢。结论YQFM可以改善心衰合并高血压大鼠的心功能、血压水平及相关生化指标,其可能的作用代谢通路为戊糖、葡萄糖醛酸转换,醚脂代谢,甘油磷脂代谢,嘌呤代谢及色氨酸代谢。Objective To investigate the pharmacodynamic effect and possible metabolic pathway of Yiqi Fumai Lyophilized Injection(YQFM)on rats with heart failure and hypertension.Methods Heart failure with hypertension rats induced by ligation of abdominal aorta and renal artery were constructed.According to the blood pressure values were randomly divided into model group and YQFM group;another rats were taken as the sham-operated group for the same operation without ligation.The drug was given once a day for 14 days by tail iv.The cardiac function of rats was detected by ultrasonic diagnostic apparatus and the blood pressure of rats was detected by eight-channel non-invasive blood pressure meter before and after administration.Serum CK-MB,cTnT,BNP,NT-proANP,LDH,Renin,Ang II,ACE1 and aGT level were detected by ELISA.LC-MS was used to analyze the differential metabolites in rat serum to find differential metabolites and metabolic pathways.Results Compared with sham-operated group,the LVEF and LVFS of the model group were significantly decreased(P<0.001),the SBP of the model group increased significantly after modeling(P<0.001),and the levels of NT-proANP,BNP,CK-MB,cTnT,LDH,Renin,aGT,ACE1 and AngII in the model group were significantly increased(P<0.001).Compared with the model group,the LVEF and LVFS of YQFM group were significantly increased(P<0.001),SBP was significantly decreased after administration of YQFM(P<0.001),the levels of NT-proANP,BNP,CK-MB,cTnT,LDH,Renin,aGT,ACE1 and AngII in serum were significantly decreased after YQFM administration(P<0.001).The possible action pathway of YQFM pathway may be pentose,glucuronate interconversions,ether lipid metabolism,glycerophospholipid metabolism,purine metabolism and tryptophan metabolism.Conclusion YQFM can improve the heart function,blood pressure level and related biochemical indexes of rats with heart failure and hypertension.The metabolic pathways may be pentose,glucuronate interconversions,ether lipid metabolism,glycerophospholipid metabolism,purine metabolism and tr

关 键 词：注射用益气复脉(冻干) 心力衰竭合并高血压 代谢组学 戊糖、葡萄糖醛酸转换 醚脂代谢 甘油磷脂代谢 嘌呤代谢 色氨酸代谢 

分 类 号：R285.5[医药卫生—中药学]