摘要
目的探讨蒙药经典方剂肉豆蔻-5对心肌梗死(MI)模型大鼠的保护作用及机制。方法将50只大鼠分为空白对照组(A组),模型对照组(B组),肉豆蒄-5高、中、低剂量干预组(C1组、C2组、C3组),各10只。除A组外,B组、C1组、C2组、C3组大鼠通过冠脉左前降支(LAD)结扎构建MI模型。C1组、C2组、C3组大鼠分别灌胃0.27,0.54,1.08 g/kg肉豆蔻-5,A组和B组大鼠灌胃等量羧甲基纤维素钠。通过检测大鼠左室射血分数(LVEF),心肌组织2,3,5-氯化三苯基四氮唑(TTC)染色、Masson染色及外周血心肌损伤标志物肌酸激酶脑型同工酶(CK-MB)和乳酸脱氢酶(LDH)水平,评价肉豆蔻-5对MI模型大鼠的保护作用。对大鼠心肌组织进行蛋白质组学检测及蛋白基因集富集分析(GSEA),明确肉豆蔻-5保护MI的作用机制。结果与B组比较,C1组大鼠的LVEF均显著升高(P<0.05);C1组、C2组大鼠的LDH和CK-MB水平均显著降低(P<0.05),心肌梗死面积占比显著缩小(P<0.05),心肌纤维化程度显著降低(P<0.05)。心肌组织蛋白质组学检测结果显示,与B组比较,C1组大鼠心肌组织中分别有522个和270个蛋白显著高表达和低表达(P<0.05)。维恩图显示,肉豆蔻-5能逆转MI模型大鼠心肌组织中169个蛋白而发挥对MI的保护作用。169个蛋白GSEA结果显示,代谢通路、氧化磷酸化通路、非酒精性脂肪肝通路、阿尔茨海默病通路、帕金森病通路被显著富集(P<0.05),其中代谢通路(EnrichmentScore=0.4538,P=0.0037)和氧化磷酸化通路(EnrichmentScore=0.4928,P=0.044)与心脏功能密切相关。结论肉豆蔻-5对MI的保护作用与调控心肌代谢有关。
Objective To investigate the protective effect and mechanism of the classic Mongolian medicine formula Nutmeng-5 on myocardial infarction(MI)model rats.Methods Fifty rats were divided into the blank control group(group A),the model control group(group B),and the high-,medium-,and low-dose intervention groups(groups C1,C2,C3),with 10 rats in each group.Except for the rats in group A,MI model rats were prepared via ligation of the left anterior descending(LAD)in groups B,C1,C2,and C3.The rats in groups C1,C2,and C3 were gavaged with 0.27,0.54,1.08 g/kg of Nutmeg-5,respectively.The rats in groups A and B were gavaged with equal volume of carboxymethyl cellulose sodium.The protective effect of Nutmeg-5 on MI model rats was evaluated by detecting left ventricular ejection fraction(LVEF),myocardial tissue 2,3,5-triphenyltetrazolium chloride(TTC)staining,Masson staining,and peripheral blood myocardial injury markers such as creatine kinase-MB isoenzyme(CK-MB)and lactate dehydrogenase(LDH)levels.Proteomics detection and gene set enrichment analysis(GSEA)of protein were performed on the myocardial tissue to clarify the mechanism of Nutmeg-5 for protecting MI.Results Compared with that in group B,the LVEF in group C1 significantly increased(P<0.05),while the levels of LDH and CK-MB in groups C1 and C2 significantly reduced(P<0.05),the proportion of myocardial infarction area in groups C1 and C2 significantly reduced(P<0.05),and the degree of myocardial fibrosis in groups C1 and C2 significantly reduced(P<0.05).The proteomic analysis of myocardial tissue showed that compared with those in group B,there were 522 and 270 proteins in the myocardial tissue of rats in group C1 significantly over-expressed and low-expressed(P<0.05).The Venn diagram showed that Nutmeg-5 could reverse 169 proteins in the myocardial tissue of MI model rats and exerted a protective effect on MI.GSEA results of 169 proteins showed that significant enrichment in metabolic pathways(P<0.05),oxidative phosphorylation pathways,non-alcoholic fatty liver pat
作者
张瑶
付贺青
刘晶
聂慧娟
董玉
刘天龙
ZHANG Yao;FU Heqing;LIU Jing;NIE Huijuan;DONG Yu;LIU Tianlong(College of Pharmacy,Inner Mongolia Medical University,Hohhot,Inner Mongolia,China 010110;The Affiliated Hospital of Inner Mongolia Medical University,Hohhot,Inner Mongolia,China 010030;Key Laboratory of Clinical and Basic Research in Cardiovascular Diseases,Inner Mon-golia Medical University,Hohhot,Inner Mongolia,China 010130;Engineering Technology Research Center of Pharmacodynamic Substance and Quality Control of Mongolian Medicine in Inner Mongolia,Hohhot,Inner Mongolia,China 010110)
出处
《中国药业》
CAS
2024年第9期68-74,共7页
China Pharmaceuticals
基金
国家自然科学基金[81960048,82160058]
内蒙古自治区科技计划项目[2019GG128]
内蒙古自治区自然科学基金[2019BS08003,2021LHMS08043]
内蒙古医科大学附属医院博士启动金计划项目[NYFY BS 202114]
内蒙古自治区高等学校青年科技人才发展计划[NJYT22005]。
关键词
肉豆蔻-5
心肌梗死
基因集富集分析
氧化磷酸化
代谢通路
作用机制
Nutmeg-5
myocardial infarction
gene set enrichment analysis
oxidative phosphorylation
metabolic pathways
mechanism
