血小板衍生生长因子B链与血管新生促进移植物动脉血管病发展

The effect of platelet-derived growth factor B and angiogenesis on development of transplant arteriopathy

目的以大鼠颈总动脉移植为模型探讨移植物动脉血管病(TA)的病理生理机制。方法建立大鼠颈总动脉移植模型。受体随机分3组,同系组(n=6):Lewis至Lewis颈总动脉移植;TA组(n=7):Brown-Norway(BN)至Lewis颈总动脉移植;干预组(n=7):BN至Lewis颈总动脉移植,术后给予阿司匹林80mg/(kg·d)治疗8周。术后8周取移植动脉做病理学分析,观察动脉内膜平滑肌细胞增殖和新生毛细血管生成情况,评估内膜增生程度;免疫组织化学法检测血小板衍生生长因子B链(PDGF-B)和环氧化酶2(COX-2)的表达。结果①同系组移植动脉内膜未见增生;TA组内膜见大量的血管平滑肌细胞(VSMC)增殖,新生内膜中见丰富的新生毛细血管形成;干预组较TA组内膜增生程度减轻(P<0.05),内膜厚度减少48.0%。②PDGF-B、COX-2在同系组几乎不表达,而在TA组移植动脉内膜显著表达;干预组较TA组PDGF-B、COX-2表达下调,阳性细胞显著减少(P<0.05)。结论TA的发病是一个多途径、多机制的病理生理过程;新生内膜高表达PDGF-B和血管新生促进了TA的发展。

Objective To investigate the pathophysiologic mechanisms of transplant arteriopathy（TA） in a rat carotid transplant model. Methods Rat common carotid transplantation model was established. The recipients were divided into 3 groups randomly： Isograft group （n = 6 ）, Lewis to Lewis. TA group （n = 7 ）, Brown-Norway （BN） to Lewis intervention group （n = 7）. In the group of BN to Lewis,administered aspirin at a dose of 80 mg/（kg·d） for 8 weeks after operation. Eight weeks after operation,the grafts were harvested. Pathologic changes of grafts were analyzed,including proliferation of vascular smooth muscle cells （VSMC） and angiogenesis in intima and the degree ofintimal hyperplasia. The expression of platelet-derlved growth factor B （PDGF-B） and cycloxygenase 2 （COX-2） were determined by immunohistochemistry. Results （1）No intimal lesion was found in the transplant vessels of isograft group. In TA group,the proliferation of vascular smooth muscle cells （VSMC） was marked and abundant neocapillaries were observed in neointima. The thickness of intimal lesion of intervention group was 48.0 % less than that of TA group. （2）PDGF-B and COX-2 weren＇ t nearly expressed in isograft group, but were highly expressed in TA group. The number of PDGF-B and COX-2 positive cell in neointima of intervention group was significantly less than that of TA group （P 〈 0.05 ）. Conclusion The pathogenesis of TA is a multi-pathway and multi-mechanism pathophysiologic process. It is demonstrated that highly expression of PDGF-B and angiogenesis in neointima should promote the development of TA.