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目的:观察动脉内膜损伤后基质金属蛋白酶-1(MMP-1)的表达变化,探讨Doxy和MMP-1对动脉内膜损伤后再狭窄的影响。方法:建立大鼠颈总动脉损伤模型,治疗组用多西环素30mg·kg-·1d-1干预,免疫组化测定损伤动脉中MMP-1的表达,弹力纤维染色观察损伤动脉内膜面积、管腔面积的情况。结果:①MMP-1阳性指数于损伤后3d表达最高,以后逐渐减少,28d时达最低值,Doxy治疗组MMP-1表达的阳性指数3d,7d,14d均低于手术组(P<0.01),而28d则与手术组无明显差别(P>0.05)。②内膜面积自术后7d开始增加,28d后达最高值,管腔面积自术后7d开始减少,28d后达最低值。Doxy治疗组14d及28d内膜面积明显小于手术组,管腔面积明显大于手术组,具有显著差异(P<0.01)。结论:动脉内膜损伤后MMP-1强烈表达,Doxy可以显著降低血管损伤后前2周MMP-1的表达,提示它可能防治动脉内膜损伤后再狭窄而不需长期给药。
Objective: To observe the expression of matrix metalloproteinase-1 (MMP-1) after arterial intimal injury and to explore the effect of Doxy and MMP-1 on the restenosis after arterial intimal injury. Methods: The model of common carotid artery injury in rats was established. The treatment group was treated with doxycycline 30 mg · kg-1d-1, the expression of MMP-1 in injured arteries was detected by immunohistochemical staining, the area of injured intima was observed by elastic fiber staining , Lumen area of the situation. Results: ① The positive expression of MMP-1 was the highest at 3d after injury, then decreased gradually and reached its lowest at 28d. The positive index of MMP-1 in Doxy treatment group was lower than that in operation group 3d, 7d and 14d (P <0.01) However, there was no significant difference between the operation group and the 28th day (P> 0.05). ② The area of intima increased from the 7th day after operation, reaching the highest value after 28 days. The lumen area decreased from 7th day after operation and reached the lowest value after 28 days. In the Doxy treatment group, the intimal area on 14d and 28d was significantly smaller than that in the operation group, and the lumen area was significantly larger than that in the operation group (P <0.01). Conclusion: MMP-1 is strongly expressed after arterial intimal injury. Doxy can significantly reduce the expression of MMP-1 in the first two weeks after vascular injury, suggesting that it may prevent restenosis after arterial intimal injury without long-term administration.