芎芍胶囊对兔实验性血管再狭窄血管胶原酶基因表达的影响

目的 观察芎芍胶囊对兔实验性血管再狭窄（RS）血管胶原酶基因表达的影响，探讨芎芍胶囊干预RS的机制。方法 采用球囊剥脱兔腹主动脉内皮结合高脂饲料方法建立实验性RS的模型，80只兔随机分层分组，分为8组，即正常对照组，单纯内皮损伤组，模型3天、2周、6周组，普罗布考对照组，芎芍胶囊小剂量、大剂量组，每只10只。采用RT-PCR方法、计算机图像分析仪，观察芎芍胶囊对再狭窄过程中血管胶原酶基因表达的影响，结合病理形态学和胶原的变化探讨芎芍胶囊改善血管重构预防RS的机理。结果 模型2周时管腔出现代偿性扩张，至6周时管腔却明显缩小，增殖指数明显升高。各用药组在抑制内膜增殖方面以芎芍大剂量组及普罗布考对照组尤为明显。模型2周时内膜胶原堆积不明显，但胶原总量增加，并达到高峰。6周时，内膜胶原逐渐堆积达到高峰。各用药组内膜胶原减少，中、外膜胶原总量减少，以芎芍大剂量组最明显。在正常对照及模型各组，基质金属蛋白酶-1（MMP-1） mRNA有弱表达，芎芍大剂量组与模型6周组比较差异有统计学意义（P＜0.05）。结论 芎芍胶囊可明显增强MMP 1mRNA在损伤血管部位的表达，提示芎芍胶囊预防RS可能与上调MMP-1mRNA的表达，增加胶原的降解，减少胶原在血管壁的沉积有关。

Effects of Xiongshao Capsule on Blood Vessel Collagenase Gene Expression in Experimental Rabbits with Arterial Restenosis

OBJECTIVE: To observe the effects of Xiongshao Capsule (XSC) on blood vessel collagenase gene expression in experimental rabbits with arterial restenosis, and to probe its mechanisms for preventing restenosis. METHODS: Restenosis rabbit model was established by injuring endothelium of abdominal aorta by balloon dilation and feeding with high fatty diet for 6 weeks. Eighty rabbits were randomly allocated into 8 groups, Group A, normal rabbit for control; Group B, rabbit with simple injured arterial endothelium; Group C, model rabbits at different times after modeling (3 days for Group C1, 2 weeks for Group C2, and 6 weeks for Group C3); Group D, model rabbit treated with Probucol for 6 weeks; Group E and F, model rabbit treated with small and large dose of XSC respectively. The effect of XSC on collagenase gene expression during the course of restenosis was observed adopting RT-PCR method and computer image analyzer, and its mechanisms in preventing RS were probed by combined analyzing the change of collagen and patho-morphological examination. RESULTS: Compensatory dilation of lumens appeared at the end of the 2nd week; while 6 weeks after modeling, the diameters of lumens obviously diminished with an apparently increased proliferation index. The cell proliferation inhibiting effect in Group D and F was significant. The total amount of collagen increased and reached the peak at the 2nd week but without conspicuous accumulation on intima, which increased gradually and reached its peak at the 6th week. In Group D-F, especially in Group F, the amount of collagen in vascular wall (intima, media and externa) was lesser than that in Groups C. MMP-1 mRNA showed weak expression in Group A and Group C1-C3; significant difference only existed in comparing Group F with C3 (P < 0.05). CONCLUSION: XSC could markedly increase the MMP-1 mRNA expression in injured portion of vessels, suggesting that its action in preventing RS might be related with the up-regulating of MMP-1 mRNA expression, increasing collagen degradation and reducing collagen deposition in vascular wall.