天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (2): 158-161.doi: 10.11958/j.issn.0253-9896.2015.02.012

• 实验研究 • 上一篇    下一篇

伊马替尼对兔颈动脉内膜增生的作用及机制研究

路雅茹 1 ,于珍 2 ,杨万松3 ,崔丽 3 ,李广平 3△   

  1.  1天津市胸科医院心内科 （邮编300222）； 2中国医学科学院血液病医院； 3天津市心血管病离子与分子机能重点实验室， 天津医科大学第二医院心脏科， 天津心脏病学研究所
  • 收稿日期:2014-04-15 修回日期:2014-10-06 出版日期:2015-02-15 发布日期:2015-02-27
  • 通讯作者: 李广平 E-mail:drlyr@163.com
  • 基金资助:
    天津市卫生局科技基金资助项目 （2013KZ079）

Effect and mechanism of Imatinib mesilate on intimal hyperplasia of rabbit carotid artery after ballon injury

  • Received:2014-04-15 Revised:2014-10-06 Published:2015-02-15 Online:2015-02-27

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摘要： 摘要： 目的 探讨伊马替尼对动脉球囊损伤后新生内膜的作用及机制。方法 长耳白兔 30 只， 按随机数字表法分为 A、 B、 C 组， 分别于右侧颈动脉球囊拉伤后给予 0、 25、 50 mg/kg 伊马替尼灌胃 1 次/d， 连续用药 14 d 处死。取双侧颈动脉行 HE 及免疫组化染色 A 组左侧颈动脉为对照组； 逆转录 PCR 检测血小板衍生生长因子 （PDGF） -B 及受体 PDGFR-β mRNA 水平。ELISA 法检测 PDGF-BB 血浆水平。结果 （1） 术后新生内膜厚度、 面积、 内/中膜厚度及面积比值较对照组均增加 （P＜0.05）。（2） 术侧组织 PDGF-B mRNA 水平 A 组高于 B 组及 C 组 （2.961±0.686、 1.957±0.545、 1.879±0.636， F=8.353， P＜0.01）； PDGFR-β mRNA 水平仅 C 组高于 A 组 （1.236±0.356 vs 0.708±0.372， P＜0.01）。（3） 各组术后血浆 PDGF-BB 水平均高于术前 （P＜0.01）， 且 A 组>B 组>C 组 （ng/L： 23.464±3.542、 19.504± 2.454、 16.588±1.207， F=17.322， P＜0.05）。（4）血浆 PDGF-BB 水平与 PDGF-B mRNA 水平正相关（r=0.806， P＜ 0.01）。结论 伊马替尼通过抑制PDGF-B mRNA 表达而抑制动脉内膜损伤后新生内膜过度增生。

关键词: 颈动脉损伤； 血管内膜； 甲磺酸盐类； 血小板源性生长因子； 受体, 血小板源生长因子β； 伊马替尼

Abstract: Abstract： Objective To investigate the effect and mechanism of Imatinib mesilate (Imatinib) on intimal hyperplasia of rabbit carotid arteries after balloon injury. Methods Thirty adult Newzealand rabbits were randomly divided into three groups: group A, B and C. Their right carotid arteries were injuried then administered with 0, 25 or 50 mg/kg of Imatinib dai⁃ ly for 14 consecutive days when the rabbits were sacrificed. The carotid arteries were harvested and sectioned for HE-stain⁃ ing and immunohistochemisty staining. Real-Time PCR was used to examine transcription levels of PDGF-B and PDGFR-β mRNA. The plasma level of PDGF-BB was assayed by ELISA. Results Arterial intimal hyperplasia and stenosis following balloon injury were seen in three groups. Thickness and area of neointima, ratio of thickness of intima to media, ratio of area of intima to media and mRNA level of PDGF-β are all higher in group A than those in group B than those in group C (P＜ 0.01). By contrast, the mRNA transcription level of PDGFR- β increased significantly in group C than that in group A (1.236±0.356 vs 0.708±0.372; t=2.91; P＜0.01). Plasma level of PDGF-BB increased in all three groups after balloon injury than that in the baseline (P＜0.01). The transcription level of PDGF-BB is higher in group A than that in group B and in group C (ng/L:23.464±3.542, 19.504±2.454, 16.588±1.207, F=17.322, P＜0.05). There was no difference between group B and C. There was positive correlation between mRNA transcription level of PDGF-B and plasma level of PDGF-BB (r= 0.806, P＜0.01). Conclusion Vascular injury can cause intimal hyperplasia and increased PDGF-B mRNA transcription. Imatinib mesilate could inhibit the intimal hyperplasia through down regulating PDGF-B mRNA transcription.

Key words: carotid artery injuries, tunica intima, mesylates, platelet-derived growth factor, receptor, platelet-derived growth factor beta, Imatinib mesilate