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目的研究炎症因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)对人冠脉平滑肌细胞表达基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶组织抑制剂-1(TIMP-1)的影响。方法①应用20μg/L的IL-1β、10μg/L的IL-6刺激人冠脉平滑肌细胞,分别在共同培养0、2、4、8、24、36h后收集细胞。②应用不同浓度的IL-1β(0、5、20、40μg/L)、IL-6(0、5、10、50μg/L)刺激人冠脉平滑肌细胞,共同培养6h后收集细胞。③应用实时荧光定量PCR的方法检测细胞内MMP-3和TIMMP-1基因的表达量。结果同剂量IL-1β、IL-6刺激下,MMP-3的表达量在2h时就开始上调,8h达高峰,而后开始下降;在不同剂量IL-1β、IL-6刺激下,MMP-3的表达量在实验剂量范围内随着IL-1β、IL-6的剂量加大呈上升趋势(IL-1β:r=0.907,P=0.000;IL-6:r=0.919,P=0.000)。而TIMP-1表达量在2h时就开始下调,IL-1β刺激下在8h左右达最低,IL-6刺激下在4h左右达最低,而后开始上升;在不同剂量IL-1β、IL-6刺激下,TIMP-1的表达量在实验剂量范围内随着IL-1β、IL-6的剂量加大呈下降趋势(IL-1β:r=-0.768,P=0.004;IL-6:r=-0.799,P=0.002)。结论炎症因子IL-1β、IL-6对冠脉平滑肌细胞中斑块稳定相关标记物MMP-3、TIMP-1表达的影响,可能是炎症在急性冠脉综合征的发生发展中起非常重要作用的机制之一。
Objective To investigate the effects of interleukin-1β (IL-1β) and interleukin-6 (IL-6) on the expression of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase- 1 (TIMP-1) effects. Methods ① Human coronary artery smooth muscle cells were stimulated with 20 μg / L IL-1β and 10 μg / L IL-6. Cells were harvested at 0, 2, 4, 8, 24 and 36 h after co-culture. ② The human coronary artery smooth muscle cells were stimulated with different concentrations of IL-1β (0, 5, 20, 40μg / L) and IL-6 (0,5,10,50μg / L) ③ Real-time fluorescence quantitative PCR was used to detect the expression of MMP-3 and TIMMP-1 in cells. Results The expression of MMP-3 began to increase at 2h after stimulation with IL-1β and IL-6, reached its peak at 8h and then began to decrease. Under the stimulation of IL-1β and IL-6, the expression of MMP-3 (IL-1β: r = 0.907, P = 0.000; IL-6: r = 0.919, P = 0.000) increased with the dose of IL-1β and IL-6 in the experimental dose range. However, the expression of TIMP-1 began to decrease at 2h, reached the lowest level at 8h after stimulation with IL-1β, reached the lowest at 4h after stimulation with IL-6, and then began to increase. After stimulated with different doses of IL-1β and IL-6 , The expression of TIMP-1 in the experimental dose range with the IL-1β, IL-6 doses increased downward trend (IL-1β: r = -0.768, P = 0.004; IL-6: r = 0.799, P = 0.002). Conclusions The effect of inflammatory cytokines IL-1β and IL-6 on the expression of MMP-3 and TIMP-1, a marker of plaque stability in coronary artery smooth muscle cells, may play an important role in the development of acute coronary syndrome One of the mechanisms.