环孢霉素A和FK506对高脂血症大鼠血管内皮的影响

Effect of FK506 and CsA on Vascular Endothelium of Hyperlipidemic Rats

目的对比观察免疫抑制剂FK506和环孢霉素A(CsA)对高脂血症大鼠血管内皮细胞的影响。方法建立高脂血症大鼠模型,分别采用CsA〔2mg/(kg.d)〕和FK506〔0.2mg/(kg.d)〕灌喂7d进行干预,取胸主动脉HE染色观察对血管内皮的影响。采用RT-PCR和免疫组织化学染色观察血管内皮细胞中血管内皮生长因子(VEGF)、补体促衰变因子(DAF)和C反应蛋白(CRP)基因和蛋白的表达;取血清检测活性氧簇(ROS)水平。结果与FK506相比,CsA损伤高脂血症大鼠血管内皮细胞,破坏血管内皮的完整性。CsA明显抑制高脂血症大鼠血管内皮中VEGF和DAF基因和蛋白的表达,上调CRP基因和蛋白的表达,而FK506无上述干预效应。此外,CsA还能明显上调ROS水平,FK506无相似的效应。结论在高脂环境中,CsA能通过VEGF/DAF和ROS/CRP途径激活补体系统,从而导致补体所介导的血管内皮细胞的损伤;而FK506对VEGF/DAF通路和ROS/CRP表达均没有明显的影响。

Objective To observe the influence of ciclosporin A（CsA） or/and FK506 on vascular endothelium of hyperlipidemic rats.Methods Hyperlipidemic rat model was established as previously described.The injury of vascular endothelium of these rats was observed after stimulation with FK506 or/and CsA.The mRNA transcription and protein expression of the vascular endothelium growth factor（VEGF）,decay-accelerating factor（DAF） and C reactive protein（CRP） in vascular endothelium of rats were measured.The serum reactive oxygen species（ROS） was detected.Results Compared with FK506,CsA was more likely to cause injury of vascular endothelium,damaging the integrity of endothelium of hyperlipidemic rats.CsA inhibited the expression of VEGF and the complement inhibitor DAF and increased the expression of CRP of vascular endothelial cells.CsA also up-regulated the serum level of ROS.FK506 showed no such impacts.Conclusion CsA can damage vascular endothelium of hyperlipidemic rats by activating the complement system induced by VEGF/DAF and ROS/CRP pathway.FK506 has no influence on the VEGF/DAF pathway and the expression of ROS/CRP.