LTB4诱导THP-1巨噬细胞MMP-9表达及在急性冠脉综合征中的意义

急性冠脉综合征（Acute Coronary Syndrom，ACS）包括急性心肌梗死（AMI）、不稳定心绞痛（UA）和心源性猝死，是严重冠状动脉粥样硬化性心脏病的表现形式，其病理生理机制尚未明确，炎症机制是目前研究的热点。白三烯B4（Leukotriene B4，LTB4）激活巨噬细胞产生炎症介质，与动脉粥样斑块不稳定关系密切；MMP-9（Matrix Metalloproteinases，MMP-9）降解细胞外基质而成为致斑块易损的重要炎症因子。

Induced MMP-9 Expression by Leukotriene B4(LTB4) in THP-1 Macrophages and Its Significance in Patients with Acute Coronary Syndrome(ACS)

Objective To observe the expression of Matrix Metalloproteinase-9 （MMP-9） induced by LTB4 in THP-1 macrophages and to explore its significance in patients with ACS.Methods Differentiated THP-1 macrophages was stimulated with LTB4 in different concentration（10-10～10-7mol/L） and for different time（0,6,12,24 and 48 hours）.RT-PCR was used to measure the expression of MMP-9 mRNA and Gelatin Zymography was used to evaluate the activity of MMP-9.Serum LTB4,MMP-9 and CRP was measured by Enzyme-linked immunosorbent assay（ELISA） in 115 patients with ACS and 105 healthy people（control group）.Results LTB4（10^-10～10^-7mol/L） upregulated MMP-9 mRNA expression in dose-and time-dependent manner and also enhanced MMP-9 activity.Serum LTB4 was significant higher in patients with acute myocardial infarction（AMI）and unstable angina pectoris（UAP） than that in control group（112.77±22.59pg/mL,86.94±14.81pg/mL and 40.5±8.85pg/mL,respectively.P〈0.01）.Besides,LTB4 was positive correlated with MMP-9（r=0.875,P〈0.001）and CRP（r=0.641,P〈0.01）.Conclusions LTB4 significantly upregulates MMP-9 expression and enhances its activity.Furthermore,levels of LTB4 and MMP9 are elevated in ACS.LTB4 and MMP-9 may play an important role in atherosclerosis by combining to form an inflammatory network and thus may contribute to the attack of ACS and serve as a potential treating target.