体外冠心病单核源巨噬细胞分泌的基质金属蛋白酶-9、组织因子的临床意义及葛根素的干预作用

Clinical Significance of Matrix Metalloproteinase-9 and Tissue Factors Secreted by Cultured Monocyte-derived Macrophage of Patients with Coronary Heart Disease in vitro and the Intervenient Effect of Puerarin on Them

目的体外培养冠心病患者的单核源巨噬细胞,探讨其分泌的基质金属蛋白酶-9(matrix metal-loproteinases-9,MMP-9)、组织因子(tissue factor,TF)的临床意义及葛根素(puerarin,Pur)的干预作用。方法入选40例患者中,急性心肌梗死(acute myocardial infarction,AMI)12例,不稳定性心绞痛(unstable angina pectoris,UAP)16例,稳定性心绞痛(stable angina pectoris,SAP)12例。冠脉造影正常者8名,均用佛波脂将提取的单核细胞诱导分化为巨噬细胞,测定上清液中MMP-9、TF的含量,并分析其与年龄、冠心病危险因素、冠脉病变评分的关系。随机留取12例急性冠脉综合征(acute coronary syndrome,ACS)患者的单核源巨噬细胞,观察不同浓度的Pur对MMP-9、TF含量及活性的干预作用。结果AMI、UAP患者MMP-9、TF的含量明显高于SAP患者和正常者(P<0.01),且MMP-9、TF含量与年龄、冠脉病变评分、危险因素无相关性;12例ACS患者Pur干预后MMP-9、TF含量及活性均较对照组有明显下降,且有浓度依赖性。结论冠心病患者单核源巨噬细胞体外分泌MMP-9、TF的水平可作为ACS病情评估的指标。Pur可抑制单核巨噬细胞MMP-9、TF的表达及其活性,在一定程度上具有稳定斑块、改善易损血液的作用。

Objective To investigate the clinical significance of matrix metalloproteinase-9 （MMP-9） and tissue factor （TF） secreted by cultured monocyte-derived macrophages （HMDM） from patients with coronary heart disease （CHD） in vitro, and to evaluate the intervenient effect of puerarin （Pur） on them. Methods A total of 40 patients were enrolled, including 12 patients with acute myocardial infarction （AMI）, 16 patients with unstable angina pectoris （UAP）, 12 patients with stable angina pectoris （SAP）. Besides, 8 healthy subjects with normal coronary arteriograph were set as controls. Monocytes acquired from their peripheral blood were incubated for 48 h and induced to differentiate into macrophages by phorbolester 12-myristate 13-acetate （PMA）, the contents of MMP-9 and TF in supernatant were assayed, and the relationship of them with patients＇ age, risk factors of CHD and coronary artery lesion scores were analyzed. HMDMs randomly from selected 12 patients with acute coronary syndrome （ACS） were arranged for observing the intervenient effects of different concentrations of Pur on the levels and activity of MMP-9 and TF. Results The levels of MMP-9 and TF in UAP and AMI patients were significantly higher than those in SAP patients and healthy subjects （P 〈 0.01）, but no statistical correlation was found between levels of MMP-9 and TF with different CHD risk factors, as well as patients＇ age and coronary artery lesion scores. The levels and activity of MMP-9 and TF in the 12 ACS patients were significantly decreased in a dose-dependent manner after Pur intervention when compared with the controt group. Conclusion The levels of MMP-9 and TF secreted in vitro by HMDM from CHD patients could be taken as indexes for evaluating patient＇s condition of ACS. Pur can inhibit the expression and theactivity of MMP-9 and TF secreted by HMDM, stabilize the plaque and improve the vulnerability of blood to certain extent.