首页|茯苓酸调节CCL2-CCR2信号轴对急性心肌梗死大鼠心肌损伤的影响

茯苓酸调节CCL2-CCR2信号轴对急性心肌梗死大鼠心肌损伤的影响

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目的 探讨茯苓酸对急性心肌梗死(AMI)大鼠心肌损伤的影响,以及单核细胞趋化蛋白-1(MCP-1/CCL2)-CC趋化因子受体 2(CCR2)信号轴发挥的作用.方法 采用左前降支结扎法构建AMI大鼠模型,将造模成功大鼠分为模型组,低、中、高剂量茯苓酸组,每组 15 只,另取 15 只大鼠作为假手术组;药物干预 14d后,小动物超声仪检测心功能相关指标变化;ELISA法检测血清炎性因子水平;HE染色检测心肌组织病理损伤;TUNEL染色观察心肌细胞凋亡;Western blot检测心肌组织CCL2、CCR2、Caspase-3 蛋白表达水平.结果 与假手术组相比,模型组大鼠心肌组织结构被严重破坏,有大量炎性细胞浸润,心功能相关指标左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、血清中炎性因子IL-6、TNF-α、IL-1β水平、心肌细胞TUNEL阳性率、心肌组织CCL2、CCR2、Caspase-3 蛋白表达水平均显著升高,左心室射血指标(LVEF)、左心室短轴缩短率(LVFS)显著降低(P<0.05);与模型组相比,低、中、高剂量茯苓酸组大鼠心肌组织结构逐渐恢复,炎性细胞浸润减轻,心功能指标LVEDD、LVESD、血清中炎症因子IL-6、TNF-α、IL-1β水平、心肌细胞TUNEL阳性率、心肌组织CCL2、CCR2、Caspase-3蛋白表达水平均显著降低,LVEF、LVFS显著升高,呈剂量依赖性(P<0.05).结论 茯苓酸可能通过调节CCL2-CCR2 信号轴减轻AMI大鼠心肌损伤.
Impacts of pachymic acid on myocardial injury in rats with acute myocardial infarction by regulating the CCL2-CCR2 signaling pathway
Objective To investigate the impacts of pachymic acid on myocardial injury in rats with acute myocardial infarction(AMI),and the role of the monocyte chemoattractant protein-1/CC-motif chemokine ligand 2(MCP-1/CCL2)-chemokine receptor 2(CCR2)signaling pathway.Methods The AMI rat model was established by ligation of the left anterior descending branch,and the rats were grouped into model groups,and low-dose,medium-dose and high-dose pachymic acid groups,with 15 rats in each group.Another 15 rats were taken as the sham operation group.After 14 days of drug intervention,indicators associated with cardiac function were detected using a small animal ultrasound system.The enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of inflammatory factors.The hematoxylin and eosin(H&E)staining was applied to detect pathological damage in myocardial tissue.The terminal deoxynucleotidyl transferase dUTP nick end-labeling(TUNEL)staining was applied to observe the apoptosis of cardiomyocytes.Western blot was applied to detect the protein levels of CCL2,CCR2,and Caspase-3 in myocardial tissue.Results Compared with those of the sham surgery group,rats in the model group presented severe damages to the rat myocardium,massive infiltration of inflammatory cells,significantly higher indicators associated with cardiac function like the left ventricular end diastolic diameter(LVEDD)and left ventricular end systolic diameter(LVESD),serum levels of inflammatory factors(interleukin 6[IL-6],tumor necrosis factor-alpha[TNF-α]and interleukin-1beta[IL-1β]),TUNEL positive rate of myocardial cells,and protein levels of CCL2,CCR2 and Caspase-3 in myocardial tissues and significantly lower left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)(P<0.05).Compared with those of the model group,rats in low-dose,medium-dose and high-dose pachymic acid groups presented gradually recovered myocardium,alleviated infiltration of inflammatory cells,significantly decreased LVEDD,LVESD,serum levels of IL-6,TNF-α and IL-1β,TUNEL positive rate of myocardial cells,and protein levels of CCL2,CCR2 and Caspase-3 in myocardial tissues and significantly higher LVEF and LVFS in a dose-dependent manner(P<0.05).Conclusion Pachymic acid may alleviate myocardial injury in AMI rats by regulating the CCL2-CCR2 signaling pathway.

pachymic acidCC-motif chemokine ligand 2-chemokine receptor 2(CCL2-CCR2)acute myocardial infarctionmyocardial damage

赖震宇、赵展庆、符妹垂

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571700 海南省儋州市,海南西部中心医院重症医学科

571700 海南省儋州市,海南西部中心医院超声科

茯苓酸 CCL2-CCR2 急性心肌梗死 心肌损伤

海南省自然科学基金面上项目

820MS154

2024

河北医药
河北省医学情报研究所

河北医药

CSTPCD
影响因子:1.075
ISSN:1002-7386
年,卷(期):2024.46(5)
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