适度铜缺乏对大鼠颈动脉内皮剥脱术后MMP-9表达和活性的影响  

Influence of moderate copper deficiency on expression and activity of MMP-9 and restenosis in balloon-injured rat carotid arteries

作　　者：周景昱[1] 郭文怡[1] 周宏志[1] 贾国良[1] 张荣庆[1] 

机构地区：[1]第四军医大学西京医院心内科,陕西西安710033

出　　处：《第四军医大学学报》2006年第13期1211-1213,共3页Journal of the Fourth Military Medical University

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（MMP-9）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2wk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（1，3，7，14d），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1g／L明胶的SDS-PAGE非变性凝胶电泳检测各点损伤的颈总动脉组织MMP-9活性，Western blot法检测MMP-9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1～7d，TM组MMP-9活性显著低于对照组，TM组MMP-9蛋白表达水平也较对照组明显降低（P〈0．01）．结论：TM诱导的适度铜缺乏能够显著抑制MMP-9的表达和活性，这可能是起抑制血管球囊损伤术后再狭窄的机制之一．AIM： To study the influence of moderate copper deficiency induced by tetrathiomolybdate （TM） on expression and activity of matrix metalloproteinases-9 （MMP-9） and restenosis in balloon-injured rat carotid arteries. METHODS： Male Sprague- Dawley 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 TM-treated 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. TM-treated rats were administrated TM daily after injury. The extent of neointimal thickening was evaluated. Western blot and gelatin-zymography were used to detect the expression and activity of MMP-9. RESULTS： Compared with the control group, the extent of neointimal hyperplasia in TM- treated rats was significantly reduced 2 weeks after injury. The expression and activity of MMP-9 were lower significantly in TM- treated rats than those in control rats from 1 to 7 d （ P 〈 0.01 ）. CONCLUSION ： The oral administration of the Cu^2＋ chelator TM could reduce neointimal thickening after balloon injury in the rat. And the expression and activity of MMP-9 were significantly suppressed by moderate copper deficiency induced by TM.

关 键 词：基质金属蛋白酶-9 铜 四硫钼酸盐 再狭窄 

分 类 号：R543[医药卫生—心血管疾病]