实验家兔血管球囊损伤后血管平滑肌细胞增殖和迁移及通心络对其影响

目的　探讨通心络对兔血管球囊损伤后血管平滑肌细胞 (VSMC)增殖和迁移的影响及其可能机制。方法　新西兰大白兔 6 4只 ,普食饲养 ,随机分为假手术组、对照组和通心络组 ,并分别于术前以及术后即刻及第 1、2、4周留取各组受损动脉标本和手术前后血液标本 ,分别行病理、电镜、RT PCR检验及血清NO浓度测定。结果　 ( 1)术后对照组新生内膜明显增厚 ,内含大量增殖、迁移的VSMC ,VSMC呈典型的“合成型”表现 ,血管腔狭窄 ;通心络组以上改变较同期对照组显著减轻。 ( 2 )对照组新生内膜面积、内膜增生指数和增殖细胞核抗原 (PCNA)增殖指数均显著高于通心络组 (P <0 .0 1) ,但管腔面积和管腔狭窄指数均显著小于通心络组 ( P <0 .0 1)。 ( 3)对照组PCNA、基质金属蛋白酶 2 (MMP 2 )、MMP 3和血小板源性生长因子 BB(PDGF BB)的免疫组化及RT PCR表达均显著高于通心络组 ,而组织抑制因子 1(TIMP 1)的表达则相对低于通心络组。 ( 4 )术后对照组血清NO浓度显著低于通心络组 ( P<0 .0 5 )。结论　通心络能明显抑制球囊损伤后VSMC增殖和迁移 ,阻止内膜增生 ,防止血管狭窄等作用

Effect of Tongxinluo on VSMC proliferation and migration after balloon-induced vascular injury in rabbits

Objective To investigate the influence of Tongxinluo on vascular smooth muscle cell(VSMC) proliferation and migration after balloon-induced vascular injury in rabbits.Methods 64 healthy male New Zealand rabbits were randomly divided into 3 groups.In sham operation group the femoral arteries were ligated;in control group the intima of right abdomi-ilium artery was damaged by balloon; in Tongxinluo group the same operation as that of control group was made and was given Tongxinluo 3 days before the injury. The specimens and serum were collected on the instant,1st,2nd,and 4th week after operation for the detections of pathology, electron microscope, RT PCR and serum levels of NO.Results (1)The intima became thicker, vessel lumen grew stenosed significantly, and VSMC showed "synthetic" expression in control group. The changes were reduced significantly in Tongxinluo group.(2)The area of neonatal intima and the intima proliferation index and PCNA in control group were significantly higher than those of Tongxinluo group (P<0.01),however, the area of vascular lumen and the index of lumen stenosis in control group were obviously smaller than those of Tongxinluo group(P<0.01).(3)PCNA proliferation index and the expression levels of MMP 2,MMP 3,PDGF BB in control group were all greater than those of Tongxinluo group.(4)The serum level of NO after operation in Tongxinluo group was significantly higher than that of control group(P<0.05).Conclusion Tongxinluo can inhibit the proliferation and migration of VSMC so as to prevent intimal hyperplasia and vessel stenosis,which may be mediated by improving the endothelial function,inhibiting the expression and activation of MMPs and PDGF,and modulating the balance of MMPs/TIMPs.