摘要
心肌梗死在外科手术治疗中常伴随着心肌缺血再灌注损伤(MI/RI),影响术后患者的正常生活。丹红注射液(DHI)已在临床中被广泛用来治疗冠心病和心绞痛等疾病,但其对MI/RI的治疗效果仍需进一步研究。本研究旨在探讨DHI抗MI/RI的药效作用成分及其作用机制。通过化学分离的方法,从DHI中得到其中的初生代谢物组分(PM)和次生代谢物组分(SM),通过建立大鼠心肌缺血再灌注损伤模型并分别给药,验证DHI、PM和SM的药效作用。实验结果表明DHI、PM和SM能够纠正扩张的心脏结构,还可以下调补体C2的表达以减轻炎症反应,通过上调环氧合酶(COX)的表达减少活性氧(ROS)的产生以及通过抑制脂肪酸代谢和刺激糖代谢恢复正常能量供应来改善心脏功能。此外,DHI和SM还可以通过下调Ca^(2+)/钙调素依赖性蛋白激酶II(CaMKII)的表达来减轻因钙超载引起的炎症反应和氧化应激。这些发现可能为中药注射剂的质量控制和安全性评价提供依据,并为心血管疾病的预防和治疗提供新思路。
Objective:The surgical treatment of myocardial infarction often causes myocardial ischemia–reperfusion injury(MI/RI).Danhong injection(DHI)has curative effects on coronary heart disease and angina pectoris.However,its therapeutic effects on MI/RI still require further validation.This study aims to investigate the components involved and mechanism of action of DHI against MI/RI.Methods:Primary metabolites(PM)and secondary metabolites(SM)were isolated from DHI.We established a rat model of MI/RI by administering PM,SM,and DHI.Cardiac morphology and functional parameters were evaluated using cardiac ultrasound.The metabolic effects of PM,SM,and DHI in the serum and myocardial tissue on MI/RI were investigated using 1hydrogen-nuclear magnetic resonance.Results:Our study showed that DHI,PM,and SM could improve cardiac function by correcting the dilated cardiac structure,alleviating inflammation by downregulating complement C2 expression,reducing reactive oxygen species(ROS)production by upregulating cyclooxygenase expression,and restoring normal energy supply by inhibiting fatty acid metabolism and stimulating glycometabolism.In addition,DHI and SM could attenuate the calcium overload and trigger an inflammatory response and oxidative stress by downregulating Ca^(2+)/calmodulin-dependent protein kinase II expression.Conclusions:This study suggests that DHI and its components exerts resistance against MI/RI by ameliorating cardiac dysfunction,energy metabolism,and oxidative stress.
作者
雷鹏
Charity Ngina Mwangi
曹远林
陈景瑞
黄钰婷
王跃飞
朱彦
樊官伟
姜苗苗
Peng Lei;Charity Ngina Mwangi;Yuanlin Cao;Jingrui Chen;Yuting Huang;Yuefei Wang;Yan Zhu;Guanwei Fan;Miaomiao Jiang(State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin,China;Pan African University Life and Earth Sciences Institute(Including Health and Agriculture)-University of Ibadan,Ibadan,Oyo State,Nigeria;National Phytotherapeutics Research Centre Kenyatta University,Nairobi,Kenya;First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin,China)
基金
This work was supported by the Tianjin Science and technology project(20ZYJDJC00120)
the National Key Research and Development Project of China(2018YFC1707403)
the Natural Science Foundation of Tianjin(18JCZDJC97700)
the Natural Science Foundation of China(81573547).
关键词
丹红注射液
心肌缺血再灌注损伤
初生代谢物组分
次生代谢物
Danhong injection
Myocardial ischemia–reperfusion injury
Primary metabolites
Secondary metabolites
