School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
R&D Department, Hubei Minkang Pharmaceutical Group Co. Ltd., Wuhan 430040, China.
Aging (Albany NY). 2022 Oct 3;14(19):7877-7889. doi: 10.18632/aging.204314.
This study aims to explore the role of hyperlipidemia in the mobilization of bone marrow (BM) endothelial progenitor cells (EPCs) induced by acute myocardial ischemia (AMI). To establish the hyperlipidemia complicated with AMI (HL-AMI) model, SD rats were intragastrically administered the high-fat emulsion for 4 weeks. Then their left anterior descending arteries were ligated. Rats in each group were randomly subdivided into seven subgroups. During 1st ~ 7th day following AMI modeling, rats in 1st ~ 7th subgroups were selected to be phlebotomized from their celiac artery after being anesthetized by pentobarbitone in turn. The quantity of circulating EPCs (CEPCs) was detected by flow cytometry, the expression of VEGF, eNOS, NO, MMP-9 in myocardial tissue was analyzed by western blot, and their plasma level was assayed by ELISA. Dynamic curves were plotted using these data. Within 7 days following AMI, compared with the AMI rats, in the HL-AMI rats, the myocardial infarct size, the plasma activity of CK, CK-MB, and the collagen deposition all remained at the higher levels; meanwhile, these rats showed more significant decreases in the count of CEPCs, the plasma level of VEGF etc., and their expression in myocardial tissue ( < 0.05 or < 0.01). Our study showed that hyperlipidemia may attenuate the mobilization of BM EPCs induced by AMI via VEGF/eNOS/NO/MMP-9 signal pathway, which might partly account for hyperlipidemia hampering the repairs of AMI-induced cardiac injury.
本研究旨在探讨高脂血症在急性心肌缺血（AMI）诱导骨髓内皮祖细胞（EPC）动员中的作用。建立高脂血症合并 AMI（HL-AMI）模型，SD 大鼠连续 4 周灌胃高脂乳剂，结扎左前降支。每组大鼠随机分为 7 个亚组。在 AMI 模型建立后的第 1 天至第 7 天，各组大鼠依次麻醉后经腹腔动脉采血，用流式细胞术检测循环 EPC（CEPC）数量，用 Western blot 分析心肌组织中 VEGF、eNOS、NO、MMP-9 的表达，用 ELISA 法检测其血浆水平。用这些数据绘制动态曲线。在 AMI 后 7 天内，与 AMI 大鼠相比，HL-AMI 大鼠的心肌梗死面积、血浆 CK、CK-MB 活性和胶原沉积仍处于较高水平；同时，CEPC 计数、VEGF 等血浆水平及其在心肌组织中的表达均显著降低（<0.05 或<0.01）。我们的研究表明，高脂血症可能通过 VEGF/eNOS/NO/MMP-9 信号通路减弱 AMI 诱导的 BM EPC 动员，这可能部分解释了高脂血症阻碍 AMI 诱导的心脏损伤修复的机制。
