COX-2及其选择性抑制剂对大鼠颈动脉球囊损伤后新生内膜增殖的影响  

Effect of cyclooxygenase-2 and its selective inhibitors on neointimal proliferation after balloon injury in rat carotid artery

作　　者：时景文[1] 白锋[1] 吴强[1] 孙守刚[1] 常鹏[1] 许广莉[1] 张小卫[1] 林欣[1] 余静[1] 胡浩[1] 郭雪娅[1] 

机构地区：[1]兰州大学第二临床医院,兰州730000

出　　处：《山东医药》2012年第48期17-19,I0002,共4页Shandong Medical Journal

基　　金：甘肃省自然科学基金资助项目(1010RJZA101)

摘　　要：目的观察塞来昔布对大鼠球囊损伤后环氧合酶-2(COX-2)、前列腺素E2(PGE2)、内皮细胞生长因子(VEGF)动态表达的影响及其与新生内膜增殖和血管再狭窄的关系,并探讨其发生的可能机制。方法 60只SD雄性大鼠随机分为阴性对照组(A组)、阳性对照组(B组)和损伤给药组(C组),每组分为6 h、7 d、14 d、28 d亚组,分别用荧光定量PCR检测组织中COX-2、PGE2mRNA表达情况;ELISA检测血中VEGF浓度情况;颈动脉HE染色和血管组织病理图像分析内膜形态变化情况。结果 A组各亚组中各种检测数值及组织图像无明显变化;B组各因子表达6 h开始增高,14 d达到高峰,28 d仍有较高表达,与A组对应时段表达具有明显差异(P<0.05);C组各因子检测数值低于B组但高于A组(P<0.05)。各组组织图像显示内膜增生情况与因子表达情况基本相同。结论塞来昔布能够通过抑制COX-2在损伤血管中的表达来抑制内皮细胞的增殖,可能为预防术后再狭窄提供新途径。Objective To discuss the possible mechanism of endometrial hyperplasia and vascular restenosis with observing the dynamic change of COX-2,PGE2 and VEGF which were expressed after the damages that had been made in rat′s sacculus and celecoxib that had been delivered.Methods Sixty SD male rats were divided into three groups at random which included negative control group（A group）,positive control group（B group） and drug delivering group（C group）.Each group was to be further split into four subunits which consisted of 6 h,7 d,14 d and 28 d.Using fluorescent quantitation PCR to detect the expressions of COX-2 and PGE2 mRNA in tissues.Using ELISA to test the expression of VEGF in blood.Utilizing carotid artery and the pathological images of vascular tissue to analyze the variation of intima forms.Results The subunits in group A neither showed any obvious changes of factors of detecting data nor significant changes of images of tissue.All factors in group B started to increase after they had expressed for 6 h.All factors reached the peak expression 14 d.These factors still expressed highly when expressed 28 d.The subunits of B group was distinctly different from the corresponding expression of group A（P〈0.05）.All figures of factors in the subunits of group C were lower than those of the subunits of group B.All figures of factors in the subunits of group C were higher than those of the subunits of group A（P〈0.05）.Images of tissue in subunit of every group showed the intima hyperplasia had the same tendency with the expressions of all factors above.Conclusion Celecoxib can restrain the hyperplasia of endothelial cell by inhibiting COX-2 of expression in injured vessel,that probably provides a new way to the prevention of postoperative restenosis.

关 键 词：球囊损伤 塞来昔布 环氧合酶-2 前列前素E2 内皮细胞生长因子 

分 类 号：R541.4[医药卫生—心血管疾病]