伊马替尼对兔颈动脉内膜增生的作用及机制研究  

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

作　　者：路雅茹[1] 于珍 杨万松[3] 崔丽[3] 李广平[3] 

机构地区：[1]天津市胸科医院心内科,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

出　　处：《天津医药》2015年第2期158-161,I0003,共5页Tianjin Medical Journal

基　　金：天津市卫生局科技基金资助项目(2013KZ079)

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-βm RNA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 m RNA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-βm RNA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 m RNA水平正相关(r=0.806,P<0.01)。结论伊马替尼通过抑制PDGF-B m RNA表达而抑制动脉内膜损伤后新生内膜过度增生。Objective To investigate the effect and mechanism of Imatinib mesilate（Imatinib） on intimal hyperplasiaof rabbit carotid arteries after balloon injury. Methods Thirty adult Newzealand rabbits were randomly divided into threegroups： 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-βmRNA. The plasma level of PDGF-BB was assayed by ELISA. Results Arterial intimal hyperplasia and stenosis followingballoon injury were seen in three groups. Thickness and area of neointima, ratio of thickness of intima to media, ratio of areaof 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 injurythan that in the baseline（P〈0.01）. The transcription level of PDGF-BB is higher in group A than that in group B and ingroup 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 Band 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.

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 

分 类 号：R541.4[医药卫生—心血管疾病]