e0545 Research on inhibiting vascular remodelling of Captopril and Xuefuzhuyu Capsule on the basis of restraining activation and migration of adventitial fibriblasts

Background Vascular remodelling is the common pathophysiological basis of artherosclerosis, hypertension and coronary artery disease, et al. It is also one of pathogenesis mechanisms which causes target organs damage and dysfunction. Now, new evidences show that the vascular adventitia may be involved in the formation of vascular remodelling. The activation and migrating to the intima of vascular adventitial fibroblasts is one of the important reasons leading to intimal thickening and stenosis. Objective To observe inhibition of ACEI drugs Captopril and Chinese medicine Xuefuzhuyu Capsule to vascular remodelling and adventitial fibriblasts activating and migrating. Methods 1. The intima of left carotid common arteries was denudated by balloon injury. Animals with the percutaneous transluminal angioplasty (PTA) were divided into five groups at random: sham, model, Captopril and Xuefuzhuyu group, which including 8 rats. The injured sections were taken out and made into specimens for HE staining to observe vascular wall thickness, area and vascular stricture rate after rats had been drenched for 28d. 2. It was adopted that primary culture of, vascular adventitial fibroblasts and TGFβ1-induced (10 ng/ml) model. Rats were randomly divided into normal group, Captopril group and Xuefuzhuyu group. Arterial blood were collected after drenching drug 7d and drug serums effected on the TGFβ1-induced fibroblasts for 48 h. The α-SM-actin expression changes were detected by the western blot method and cell migration rate by cell scratch method. Results 1. Effects of drugs on indexes of vascular remodelling: Neointimal thickness of Xuefuzhuyu group significantly was reduced than that of model group (18.92±4.77 μm vs 52.11±21.65 μm, p<0.01), and so did neointimal area (0.048±0.013 mm2 vs 0.130±0.049 mm2, p<0.01). At the same time, vascular stricture rate of Xuefuzhuyu group was obviously decreased compared with model group (8.910±2.120 vs 22.85±9.763%, p<0.01). These three indexes of Captopril group were no statistically significant differences through lessening trend. 2. Effect of drug serum on expression of α-SM-actin of TGFβ1-induced fibroblasts: Light density values (OD) of normal controls, TGF-β1, Captopril and Xuefuzhuyu group were 0.852±0.0223, 1.071±0.0486, 0.889±0.0310 and 0.858±0.0204 respectively, and values of captopril and Xuefuzhuyu group were significantly reduced compared with TGF-β1 group (p<0.01). 3. Effect of drug serum on mobility of TGFβ1-induced fibroblasts: Cell migration rates of captopril and Xuefuzhuyu group lowered significantly than that of TGF-β1 group (0.140±0.0687 and 0.108±0.0435 vs 1.000±0.0000, p<0.01). Conclusions 1. Both captopril and Xuefuzhuyu Capsule inhibit vascular remodelling to a certain extent. Animal experiments shows that more benefits can be obtained from the Xuefuzhuyu than Captopril. 2. Drug serums of two drugs can inhibit activation and migration of adventitial fibriblasts, which may be one of mechanisms of inhibiting vascular remodelling.