首页|基于血清代谢组学探究蛭龙活血通瘀胶囊对心肌缺血再灌注损伤小鼠的保护作用及机制

基于血清代谢组学探究蛭龙活血通瘀胶囊对心肌缺血再灌注损伤小鼠的保护作用及机制

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目的 观察蛭龙活血通瘀胶囊(简称"蛭龙胶囊")对心肌缺血再灌注损伤(MIRI)小鼠的保护作用,并应用代谢组学探讨其调控机制.方法 采用随机数字表法,将 30 只C57BL/6J小鼠随机分为假手术组、模型组和蛭龙胶囊组(6.24 g/kg),每组10 只.模型组和蛭龙胶囊组采用结扎左前降支方法建立MIRI小鼠模型,假手术组只穿线不结扎.蛭龙胶囊组预给药 1 周后开始造模,造模后持续灌胃给药2 周,每日1 次.心脏彩超检测小鼠心功能[左室射血分数(LVEF)和左室缩短分数(LVFS)];采用Masson染色和TUNEL染色观察小鼠心肌纤维化和心肌细胞凋亡情况;采用酶联免疫吸附测定法测定小鼠血清乳酸脱氢酶(LDH)、脑利尿钠肽(BNP)含量;采用液相色谱-质谱法结合多元统计方法进行血清代谢物检测及鉴定分析.结果 与模型组比较,蛭龙胶囊组小鼠LVEF、LVFS升高,心脏组织结构紊乱减轻,心肌纤维化程度降低,细胞凋亡率降低,血清LDH、BNP含量降低(P<0.05).代谢组学结果表明,蛭龙胶囊干预后可明显调控30 个与MIRI相关的差异代谢物,其相关代谢途径涉及酪氨酸代谢、精氨酸与脯氨酸代谢、维生素消化吸收等 20 条通路.结论 蛭龙胶囊对MIRI有保护作用,其作用机制可能是通过调节酪氨酸代谢、精氨酸与脯氨酸代谢、维生素消化吸收等通路实现的.
Study on the protective effect and mechanism of Zhilong Huoxue Tongyu Capsule on myocardial ischemia reperfusion injury mice based on serum metabolomics
Objective To observe the protective effect of Zhilong Huoxue Tongyu Capsule(Zhilong Capsule)on myocardial ischemia reperfusion injury(MIRI)in mice,and explore its regulatory mechanism using metabolomics.Methods Using a random number table method,30 C57BL/6J mice were randomly divided into the following three groups:sham operation group,model group,and Zhilong Capsule group(6.24 g/kg),with 10 mice in each group.In mice in the model group and the Zhilong Capsule group,a mouse MIRI model was established by ligating the left anterior descending branch,while mice in the sham operation group underwent threading without ligation.The Zhilong Capsule group began modeling one week after pre-administration and continued to receive intragastric administration for two weeks after modeling once daily.The cardiac function,including the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS),was assessed by color echocardiography.The myocardial fibrosis and apoptosis were observed by Masson staining and TUNEL staining,respectively.Enzyme-linked immunosorbent assay was used to measure the serum contents of lactate dehydrogenase(LDH)and brain natriuretic peptide(BNP).Liquid chromatography-mass spectrometry combined with multivariate statistical method was performed for serum metabolite detection and identification analysis.Results Compared with the model group,the mice in the Zhilong Capsule group exhibited an increase in LVEF and LVFS,a reduction in cardiac tissue structure disorder,a decrease in myocardial fibrosis,a decrease in cell apoptosis rate,and a decrease in serum LDH and BNP contents(P<0.05).Metabolomics result showed that intervention with Zhilong Capsule significantly regulated 30 differential metabolites related to MIRI.Important metabolic pathways involved 20 pathways related to tyrosine metabolism,arginine and proline metabolism,and vitamin digestion and absorption.Conclusion Zhilong Capsule has a protective effect on MIRI,and it may achieve this effect by regulating pathways related to tyrosine metabolism,arginine and proline metabolism,and vitamin digestion and absorption.

Zhilong Huoxue Tongyu Capsulemyocardial ischemia reperfusion injuryserum metabolomicsmetabolitesmice

刘孟楠、毛琳慎、伍浩、邹沅、兰琪、薛进宜、刘平、杨思进、胡钟竞

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西南医科大学中西医结合学院·附属中医医院 泸州 646000

蛭龙活血通瘀胶囊 心肌缺血再灌注损伤 血清代谢组学 代谢产物 小鼠

国家自然科学基金面上项目四川省科技厅项目泸州市科技局项目西南医科大学项目

820743782022YFS06182023JYJ0292023ZYYQ04

2024

北京中医药大学学报
北京中医药大学

北京中医药大学学报

CSTPCD北大核心
影响因子:1.568
ISSN:1006-2157
年,卷(期):2024.47(4)
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