中文摘要：

目的 探讨CC趋化因子配体2（CCL2）在残余血小板高反应中的作用及其调控血小板的可能机制。方法纳入ST段抬高型心肌梗死（STEMI）患者40例,采用Verify Now法检测P2Y12反应单元（PRU）,根据检测结果将40例患者分为残余血小板高反应组（高反应组,n=24）和残余血小板正常反应组（正常反应组,n=16）。ELISA检测两组患者血浆中CCL2的表达,Western blotting检测血小板中CCL2和CCR2的表达,ARY003B蛋白芯片筛选经外源性CCL2刺激后血小板中磷酸化水平发生变化的激酶。Western blotting验证经CCL2刺激,或经CCR2拮抗剂（RS 102895）、p38MAPK信号通路抑制剂（SB 203580）预处理后血小板中p38MAPK和HSP27的磷酸化变化。结果 高反应组血浆中CCL2浓度、血小板中CCL2和CCR2表达均明显高于正常反应组。经外源性CCL2刺激后,芯片筛选发现p38α、HSP27的磷酸化水平增高。在CCL2刺激前,应用RS 102895或SB 203580预处理血小板,Western blotting检测显示p38MAPK和HSP27的磷酸化水平下降。结论 CCL2以自分泌/旁分泌的方式参与残余血小板高反应,CCL2可能通过p38MAPK-HSP27通路调控血小板。

英文摘要：

Objective To investigate whether chemokine CC motif 2 （CCL2） is involved in the high residual platelet response, and the mechanism of CCL2 being involved in the regulation of platelets. Methods Forty patients with ST elevation myocardial infarction （STEMI） were admitted. P2Y12 reaction unit （PKU） was detected by VerifyNow. Forty patients were divided into high platelet reactivity group （high reactivity group, n=24） and normal platelet reactivity group （normal reactivity group, n=16） according to the results of PRU detection. Plasma CCL2 concentration of the STEMI patients was examined by ELISA. The expressions of CCL2 and CCR2 in the platelets were detected by Western blotting. After CCL2 stimulation, the kinases of which phosphorylation was changed in the platelets were screened by ARY003B protein chips. The phosphorylation of p38MAPK and HSP27 in the platelets was tested by Western blotting after CCL2 stimulation in the presence or absence of CCR2 antagonist （RS 102895） or p38MAPK signal pathway inhibitor （SB 203580）. Results The plasma CCL2 concentration of high reactivity group was markedly higher than that of normal reactivity group. Moreover, compared with normal reactivity group, the expressions of CCL2 and CCR2 in the platelets of high reactivity group significantly increased. After the platelets were stimulated by CCL2, the phosphorylation of p38a and HSP27 enhanced in the platelets by protein chips screening. When KS 102895 or SB 203580 was treated before CCL2 stimulation, the phosphorylation of p38MAPK and HSP27 decreased. Conclusions CCL2 participates in high residual platelet response in an autocrine/paracrine way. CCL2/CCR2 might affect the function ofplatelets through p38MAPK- HSP27 signal pathway.