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通过阻断MCP-1实现深静脉血栓溶解及抑制巨噬细胞趋化性

Thrombolysis of deep vein thrombosis and inhibiting chemotaxis of macrophage by MCP-1 blockage.

作者信息

Wang Z-W, Wang J-J, Zhang J-Z, Xue Z-J, Miao J, Li L, Hu W-X

机构信息

Department of Vascular Surgery, The Affiliated Qingdao Hiser hospital of Qingdao University, Qingdao, Shandong Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Apr;21(7):1695-1701.

PMID:28429334
Abstract

OBJECTIVE

Deep vein thrombosis (DVT) is one common vascular complication after trauma or surgery. Macrophage plays an important role in recanalization of thrombosis and monocyte chemotactic protein 1 (MCP-1) has a potent chemotactic role for macrophage. This study investigated the role of MCP-1 and macrophage in DVT thrombolysis.

MATERIALS AND METHODS

DVT mice model was established for evaluating thrombosis grades, and divided into DVT, DVT + MCP-1 recombinant protein, and DVT + MCP-1 neutralizing antibody groups. MCP-1 mRNA and protein expression, weight/length ratio of thrombosis were tested at 1, 5, 9 and 15 day after DVT. F4/80 protein expression in thrombosis on day 9 was measured to reflect infiltration of macrophage.

RESULTS

DVT model mice had thrombosis grade at 2.47 ± 0.22 whilst no thrombosis occurred in sham group. DVT group had gradually increased MCP-1 mRNA and protein expression, which reached the peak at day 9, followed by decreased expression. Thrombosis weight/length ratio showed decreasing trends. MCP-1 protein injection significantly elevated MCP-1 expression, decreased thrombosis weight/length ratio, and elevated macrophage infiltration. Injection of MCP-1 antibody remarkably decreased MCP-1 expression, elevated thrombosis weight/length ratio and macrophage infiltration.

CONCLUSIONS

MCP-1 up-regulation participates in macrophage chemotaxis and thrombolysis after DVT formation. The blockade of MCP-1 weakens its thrombolysis effects.

摘要

目的

深静脉血栓形成(DVT)是创伤或手术后常见的血管并发症。巨噬细胞在血栓再通中起重要作用,单核细胞趋化蛋白1(MCP-1)对巨噬细胞具有强大的趋化作用。本研究探讨MCP-1和巨噬细胞在DVT溶栓中的作用。

材料与方法

建立DVT小鼠模型以评估血栓形成等级,并分为DVT组、DVT + MCP-1重组蛋白组和DVT + MCP-1中和抗体组。在DVT后第1、5、9和15天检测MCP-1 mRNA和蛋白表达、血栓重量/长度比。检测第9天血栓中F4/80蛋白表达以反映巨噬细胞浸润情况。

结果

DVT模型小鼠的血栓形成等级为2.47±0.22,而假手术组未发生血栓形成。DVT组MCP-1 mRNA和蛋白表达逐渐增加,在第9天达到峰值,随后表达下降。血栓重量/长度比呈下降趋势。注射MCP-1蛋白显著提高MCP-1表达,降低血栓重量/长度比,并增加巨噬细胞浸润。注射MCP-1抗体显著降低MCP-1表达,提高血栓重量/长度比和巨噬细胞浸润。

结论

MCP-1上调参与DVT形成后的巨噬细胞趋化和溶栓过程。阻断MCP-1会削弱其溶栓作用。

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