适度铜缺乏对大鼠颈动脉内皮剥脱术后mmp.docVIP

适度铜缺乏对大鼠颈动脉内皮剥脱术后MMP 作者：周景昱，郭文怡，周宏志，贾国良，张荣庆 【关键词】 基质金属蛋白酶 　　Influence of moderate copper deficiency on expression and activity of MMP9 and restenosis in ballooninjured rat carotid arteries 　　【Abstract】 AIM: To study the influence of moderate copper deficiency induced by tetrathiomolybdate (TM) on expression and activity of matrix metalloproteinases9 (MMP9) and restenosis in ballooninjured rat carotid arteries. METHODS: Male SpragueDawley rat were prefed distilled water or TM at a dosage of 10 mg/kg 2 weeks before balloon injury. Plasma ceruloplasmin levels were monitored, and the oral administration of TM could rapidly reduce and sustain the plasma level of ceruloplasmin in all TMtreated animals at a 70%-80% level of reduction after 2 weeks. All rats were subjected to balloon injury and then were killed at 1, 3, 7 and 14 d. TMtreated rats were administrated TM daily after injury. The extent of neointimal thickening was evaluated. Western blot and gelatinzymography were used to detect the expression and activity of MMP9. RESULTS: Compared with the control group, the extent of neointimal hyperplasia in TMtreated rats was significantly reduced 2 weeks after injury. The expression and activity of MMP9 were lower significantly in TMtreated rats than those in control rats from 1 to 7 d （P＜0.01）. CONCLUSION: The oral administration of the Cu2+ chelator TM could reduce neointimal thickening after balloon injury in the rat. And the expression and activity of MMP9 were significantly suppressed by moderate copper deficiency induced by TM. 　　【Keywords】 matrix metalloproteinases9; copper; tetrathiomolybdate; restenosis 　　【摘要】 目的：探讨四硫钼酸盐（TM）引起的适度铜缺乏对大鼠颈动脉球囊损伤后内膜增生和基质金属蛋白酶9（MMP9）活性和表达的影响. 方法：SD雄性大鼠随机分为铜缺乏组（TM组）和对照组，TM组术前2 wk及术后给予TM强饲，使血清铜蓝蛋白降至基础值的（20±2）%；对照组给予蒸馏水强饲. 每组分为5个时相点（1，3，7，14 d），建立颈总动脉球囊损伤模型，于术后相应时间点处死动物. 利用含1 g/L明胶的SDSPAGE 非变性凝胶电泳检测各点损伤的颈总动脉组织MMP9活性，Western blot法检测MMP9蛋白表达水平. 结果：TM组血管内膜增生程度较对照组显著降低，管腔无明显狭窄. 术后1~7 d，TM组MMP9活性