罗格列酮抑制大鼠颈动脉球囊损伤后新生内膜增生和基质金属蛋白酶-2的表达

基础医学与临床 ›› 2012, Vol. 32 ›› Issue (6): 687-692.

罗格列酮抑制大鼠颈动脉球囊损伤后新生内膜增生和基质金属蛋白酶-2的表达

周晓莉,雷寒

重庆医科大学附属第一医院

收稿日期:2011-12-12 修回日期:2012-03-27 出版日期:2012-06-05 发布日期:2012-05-25
通讯作者: 周晓莉 E-mail:zhouxlcq@yahoo.cn

Rosiglitazone inhibits neointimal hyperplasia and the expression of MMP-2 of carotid arteries after balloon injure in rats

Received:2011-12-12 Revised:2012-03-27 Online:2012-06-05 Published:2012-05-25
Contact: xiaoli zhou E-mail:zhouxlcq@yahoo.cn

摘要/Abstract

摘要： 摘要：目的探讨PPARγ配体罗格列酮对大鼠颈动脉球囊损伤后新生内膜增生及MMP-2和TIMP-2表达的影响。方法实验分为给药组（罗格列酮3 mg/kg?d）和对照组（生理盐水），每组n =5。用球囊血管内膜剥脱法建立大鼠颈动脉再狭窄模型。HE染色检测血管内膜与中膜的厚度比和面积比。RT-PCR和Western blotting法检测血管组织MMP-2和TIMP-2的mRNA和蛋白质的表达。结果罗格列酮明显抑制球囊损伤后血管新生内膜增生，与对照组相比，术后所有时间点上内膜与中膜的厚度比及面积比均显著减少（P <0.001）。罗格列酮组与对照组比较显著抑制球囊损伤后各时间点血管中基质金属蛋白酶-2的mRNA和蛋白的表达，术后1、7、14、28d蛋白表达由对照组的0.605 0.007、1.000 0.002、0.890 0.014和0.290 0.028降至0.310 0.014、0.525 0.021、0.405 0.007和0.081 0.004（P <0.001)。但罗格列酮对MMP-2抑制剂TIMP-2的mRNA和蛋白表达无影响。结论罗格列酮抑制大鼠颈动脉球囊损伤后新生内膜增生，其机制可能与MMP-2的表达下调及MMP-2/TIMP-2表达失衡有关。

关键词: 罗格列酮, PPARγ, 新生内膜, MMP-2, TIMP-2

Abstract: Objective To investigate the effects of PPARγ ligand rosiglitazone on neointimal hyperplasia and the expression of MMP-2 and TIMP-2 in rat carotid arteries after balloon injure. Methods Treatment group (rosiglitazone 3 mg/kg?d,n=5 ) and control group (saline,n=5) are included in the study. Vascular restenosis in rat carotid arteries was established by balloon denudation. The thickness and area ratios of intima to media (I/M and IA/MA) were measured by using hematoxylin and eosin staining. The mRNA levels and protein expression of MMP-2 and TIMP-2 in vascular tissues were measured by RT-PCR and Western-blotting, respectively. Results Both I/M and IA/MA were significantly reduced in rosiglitazone group compared to that in control group at different time points after balloon injury (P＜0.0001). Rosiglitazone markedly suppressed the mRNA and protein expression of MMP-2 in carotid arteries induced by balloon injury（P＜0.0001）. But there were no difference in the mRNA and protein expression of TIMP-2 between rosiglitazone group and control group. Conclusion This study demonstrates that rosiglitazone inhibits neointimal hyperplasia in carotid arteries after balloon injury. Our results suggest that rosiglitazone suppresses neointimal hyperplasia by modulating some taget gene transcription, down regulating MMP-2 expression and breaking the balance of MMP-2 and TIMP-2 in sequence.

Key words: Rosiglitazone, PPARγ, Neointima, MMP-2, TIMP-2

中图分类号:

R541.4

周晓莉雷寒. 罗格列酮抑制大鼠颈动脉球囊损伤后新生内膜增生和基质金属蛋白酶-2的表达[J]. 基础医学与临床, 2012, 32(6): 687-692.

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