Effects of statin on vascular diseases-inhibitory mechanism on intimal hyperplasia

观察了亲水性他汀类药物普伐他汀和脂类他汀类药物匹伐他汀对实验性正常胆固醇血症兔自体移植静脉内膜增生、血流动力学和中期因子表达的影响。分别给予普伐他汀(10 mg/kg/d)和匹伐他汀(1 mg/kg/d)。治疗开始一周后，颈动脉内植入Juglar静脉。术后2周、4周取材，观察移植静脉内膜增生情况。种植2周后，用增殖细胞核抗原和Ki-67染色检测新生内膜细胞增殖情况。此外，通过Western blotting分析了匹伐他汀对移植静脉中肝素结合生长因子Midkine表达的影响。采用免疫印迹法检测普伐他汀对人脐静脉内皮细胞和血管平滑肌细胞的影响。我们向大家展示了口服药…普伐他汀和匹伐他汀对高胆固醇血症兔移植颈动脉内膜有抑制作用，抑制颈动脉内膜细胞增殖和细胞凋亡。此外，我们还发现，普拉沙丁抑制人脐静脉内皮细胞的Rho-Kinase活性，促进内皮型一氧化氮合酶的表达，但不抑制血管平滑肌细胞的Rho-Kinase活性。对于匹伐他汀，我们发现他汀类药物在移植后的静脉移植物中显著抑制了中期因子的表达。这些新的发现清楚地表明，亲水性和脂膜性他汀类药物在体内都能抑制移植静脉的内膜增生，其中亲水性他汀类药物在体外表现出对Rho-Kinase的亲内皮细胞抑制作用，而亲脂性他汀类药物则表现出中期因子抑制作用。这些结果有力地支持了他汀类药物的临床应用，以预防搭桥后静脉移植物的内膜增生。较少

The efficacy of statin, a hydrophilic statin, pravastatin, and a lipohylic statin, pitavastatin, were evaluated on intimal hyperplasia, Rho-kinesis, and midkine expression of experimental normocholesterolemic rabbit autologous vein graft. Rabbit were fed regular rabbit chow, and pravastatin (10mg/kg/day), and pitavastatin (1mg/kg/day) was administered, respectively. A week after starting the treatment, juglar vein was implanted into the carotid artery. At 2 and 4 weeks after the operation, vein graft were harvested, and intimal hyperplasia of the vein grafts were assessed. Cell proliferation in neointima was detected by PCNA and Ki-67 stain 2 weeks after implantation. In addition, the effect of pitavastatin on midkine expression, a heparin-binding growth factor, in vein grafts was analyzed by Western blotting. And also the effect of pravastatin on human umbilical vein endothelial cells and vascular smooth muscle cells were examined by Westernblotting. We demonstrated that oral administ … More ration of both pravastatin and pitavastatin to normocholesterolemic rabbits inhibited intimal hyperplasia of carotid interposition-reversed juglar vein grafts after implantation and suppressed cell proliferation and apoptosis in theneointima. In addition, we found that pravasatatin inhibited Rho-kinase activity and accelerated endothelial nitric oxide synthase expression in human unbilical vein endothelial cells but did not inhibit Rho-kinase activity in vascular smooth muscle cells. As to pitavasatin, we found that pitavastatin inhibited midkine expression significantly in the vein grafts after implantationThese novel findings clearly demonstrated that both hydrophilic and lipohylic statin can suppress intimal hyperplasia of the vein graft in vivo, and a hydrophilic statin show endothelial cell-tropic inhibition of Rho-kinase in vitro, while a lipophilic statin show midkine inhibition. These results strongly support the clinical use of statins to prevent intimal hyperplasia of the vein graft after bypass grafting. Less