中文摘要：

目的：观察单核细胞趋化蛋白1（monocyte chemoattractant protein-1, MCP-1）与急性肺栓塞（pulmonary thromboembolism, PTE）后肺动脉高压形成的关系；探讨p38丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）特异性抑制剂SB203580对急性PTE后肺动脉高压及MCP-1表达的影响。方法：采用自体血栓回输法复制Sprague-Dawley大鼠急性PTE模型；将大鼠随机分成5组，每组观察1 h、4 h和8 h 3个时点；急性PTE模型复制前1 h，分别对MCP-1中和抗体C1142组及SB203580组进行药物预处理；在1 h、4 h和8 h检测各组肺动脉平均压力（mean pulmonary artery pressure, MPAP）和MCP-1 mRNA及蛋白表达。结果：（1）在相同时点，急性PTE组MPAP和MCP-1 mRNA及蛋白表达均较溶剂对照组显著升高（P〈005）；（2）在相同时点，C1142组及SB203580组MPAP和MCP-1 mRNA及蛋白表达均较急性PTE组显著降低（P〈005）。结论：（1）急性PTE后MCP-1的大量表达参与急性PTE性肺动脉高压的形成；（2）SB203580可能通过p38 MAPK信号转导通路，下调MCP-1表达，降低急性PTE肺动脉压力。

英文摘要：

AIM：To explore the hypothesis that initiation of pulmonary hypertension involves the up-regulation of monocyte chemoattractant protein-1 （MCP-1） in acute pulmonary thromboembolism （PTE）, and to evaluate the role of p38 mitogen-activated protein kinase （MAPK） in this process. METHODS：One hundred and fifty male SD rats were randomly divided into five groups （n=30）： normal control group, solvent control group, acute PTE group, acute PTE plus SB203580 （a p38 MAPK specific inhibitor） pretreatment group and acute PTE plus C1142 （a rodent chimeric monoclonal antibody neutralizing rat MCP-1） pretreatment group. Thirty rats in each group were further divided into 1, 4 and 8 h subgroups （n=10）. A rat model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. SB203580 or C1142, dissolved in 1% dimethyl sulfoxide （DMSO）, was administered to the animals through caudal vein 1 h prior to the beginning of acute PTE modeling. Rats in normal control group and solvent control group were injected with normal saline and 1% DMSO, respectively. The mean pulmonary artery pressure （MPAP） and the mRNA and protein expression of MCP-1 were measured at each time point. RESULTS：Acute PTE elicited significant increase in MPAP, and up-regulated the expression of MCP-1. Pretreatment with SB203580 or C1142 significantly reduced MPAP, and down-regulated the expression of MCP-1. CONCLUSION：These findings suggest that MCP-1 is involved in the formation of acute PTE-induced pulmonary hypertension, and SB203580 down-regulates the expression of MCP-1 via p38 MAPK signaling pathway, thus attenuating pulmonary hypertension.