Expression and distribution of ectopic trypsin in the atherosclerotic plaques and its potential impacts on plaque stability
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摘要: 目的:探讨动脉粥样斑块组织中异位胰蛋白酶的表达分布及其对斑块稳定性的潜在影响。方法:20只8周龄雄性新西兰白兔随机分入对照组和动脉粥样硬化实验组 (实验组), 每组10只。对照组予普通饲料, 实验组予高胆固醇高脂饲料, 持续喂养17周后处死, 切取主动脉和冠状动脉组织, 分别进行病理和生化检查。结果:实验组的主动脉及冠状动脉组织中异位胰蛋白酶、基质金属蛋白酶-9 (MMP-9) 及促炎细胞因子白细胞介素 (IL) -6、IL-β及肿瘤坏死因子α (TNF-α) 表达较对照组显著上调 (均P<0.01);激活型MMP-9 (actMMP-9) 与前体型MMP-9 (proMMP-9) 的比值显著增高 (P<0.05);粥样斑块组织内可见异位胰蛋白酶大量表达, 上调的异位胰蛋白酶与MMP-9分布一致, 均主要分布在粥样斑块中。结论:作为proMMP-9的有效激动剂, 动脉粥样斑块组织中大量表达的异位胰蛋白酶可能是引发粥样斑块炎症反应及破裂的一个重要因素。Abstract: Objective: To investigate the distribution of ectopic trypsin in atherosclerotic plaques and its potential impacts on plaque stability.Method: Twenty New Zealand male white rabbits of 8-week-old were randomized into either control group (Group C) or atherosclerotic group (Group A) which were fed with normal diet or high cholesterol and fat diet for a period of 17 weeks.The rabbits were sacrificed and the aorta and coronary arteries were separated for pathological and biochemical analysis.Result: The expression of ectopic trypsin, matrix metalloproteinase (MMP-9) and proinflammatory cytokines IL-6、IL-βand TNFαwere significantly upregulated in Group A compared to Group C (all P<0.01).The ratio of activated MMP-9 (actMMP-9) to proMMP-9 also significantly increased (P<0.05).The ectopic trypsin was highly expressed in the atherosclerotic plaques and its distribution pattern was overlapped with that of MMP-9.Conclusion: Working as a potent activator of proMMP-9, the highly expressed ectopic trypsin in the atherosclerotic plaques might be an important factor for the onset of plaque inflammation and rupture.
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