| Background and Objective—Acute coronary syndrome (ACS) is one of the acute cardiovascular disease.Common pathophysiological foundation of ACS is acute or subacute myocardial oxygen decrease because occurreding plaques based on rupture or erosion, ulcer, concurrent thrombosis, vasoconstriction, microvascular embolism in coronary atherosclerosis.Research shows that plaque ruptured is relevant to vascular endothelial dysfunction, hemodynamic instability, Smooth muscle cells (VSMC) proliferation and functional changing,apoptosis except inflammation , and MatrixMetalloproteinases (MMPS) decomposition Extracellular Matrix (ECM) and c-reactive protein (CRP) increasing.Currently macrophages,CRP and MMPS plays an important role in plaque of ACS,DanHong of chinese drug may have increased coronary artery blood flow, and reduced myocardial oxygen consumption, anti-ischemia, and lowered blood thick functions. Above evidnce shows wether it is connection among MMPS,DanHong and CRP. The aim of this study was to investigate the effects of CRP on Matrix meta1loproteinases-1 ( MMP-1 ) release from human THP-1 derived macrophages and the related signal transduction pathways.At some time,we observed MMP– 1 of changing by Chinese drug DanHong intervention. To be understanding occurrence, development and mechanism of ACS deeply. DanHong has a benefit for patients with ACS.Methods–Human mononuclear cell leukemia cell(THP - l cells) was cultured in vitro with RPMI1640 medium to be quantity to 5.0 x 10~6 / ml and placement 6 orifice plate .Human THP-1 cells were induced to differentiate into macrophages by phorbol -12myristate 13-acetate stimulation (PMA).Using enzyme immunosorbent adsorption experiment method (ELISA) determined MMP - 1 protein expression time in macrophage cell in 6, 12, 24, 48, 72 hours. Experiments were divided into four groups: control group, CRP group, BAY-117085 group (50mg/L of CRP + NF-KB inhibitor- BAY-117085),DanHong group. ELISA was employed to measure MMP-1 release from these macrophages. MMP-1 mRNA was measured by reverse transcription polymerase chain reaction (RT-PCR). And would MMP - 1 protein concentration and mRNA expression was analyzed.Results -- THP-1 cell induction into macrophages was observed under the microscope. CRP-induced MMP-1 protein secretion was found to peak in 24-hour. Compared with the control group, MMP-1 protein and mRNA expression in CRP group was markedly up-regulated in a dose-dependent manner(5mg/L,10mg/L,25 mg/L,50mg/L CRP,P<0.05). The induction about CRP increasing MMP-1 expression was reduced significantly by BAY-117085 inhibitor, (CRP group vs. CRP+ BAY-117085: P<0.01). However, the expression of MMP-1 in BAY-117085 group still remained higher than control group (P <0.01), indicating that the inhibitor can partially blocked the effect of CRP on the induction of MMP-1 expression. DanHong can reduce expression of MMP - 1 in a stage with 0ul/ml,200ul/ml,400u/ml,800ul/ml,1600ul/ml,3200ul/ml.(P < 0.05)。Conclusion-- PMA can induce suspended THP - 1 cell transformation into macrophages completely in 48 hours ,CRP promotes the expression of MMP-1 in THP-1 derived macrophages in the level of its mRNA and protein. The adjustment function may realize possibly via KB - NF signaling pathways. Dan Hong can restrain MMP - 1 secretion, and may to have a effect of stabing atheromatous plaque in CHD. |
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