Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhengzhou University, Zhengzhou, Henan 450052, China.
Chin Med J (Engl). 2013;126(10):1906-12.
Everolimus, a derivative of sirolimus, is a potent immunosuppressant that has important anti-proliferative properties. In the present study, we demonstrated the inhibiting neointimal hyperplasia in injured carotid arteries in rats by using two different doses of everolimus administrated via the oral route for a long time.
A rat model of carotid artery injury was established by balloon inflation. Eighty rats were randomly divided into the sham-operated group (n = 20), injury group (n = 20), low dosage of everolimus group (n = 20), and high dosage of everolimus group (n = 20). The low dose of everolimus (1.5 mg/kg) was given one day before injuring the carotid artery by balloon, followed by 0.75 mg/kg per day for 28 days via intragastric gavage. High dose everolimus (2.5 mg/kg) was given one day before injuring the carotid artery by balloon, followed by 1 mg/kg per day for 28 days. Expression of eukaryotic translation initiation factor 4E (eIF-4E) and phosphorylation of ribosomal protein S6 kinase 1 (P70S6K) were determined by reverse transcription-polymerase chain reaction and Western blotting analysis.
In the injured carotid artery, neointimal hyperplasia was normally observed four weeks after injury. Everolimus inhibited neointimal hyperplasia after balloon injury in a dose dependent manner. At the same time, the study demonstrated that everolimus reduced the expression of P-P70S6K, eIF-4E, transforming growth factor (TGF)-β1 and of proliferating cell nuclear antigen (PCNA).
Everolimus significantly inhibited neointimal hyperplasia of the injured carotid artery. The effect depended on dosage and was associated with the reduction of phosphorylation of P70S6K and the eIF-4E expression level.
依维莫司是西罗莫司的衍生物，是一种强效的免疫抑制剂，具有重要的抗增殖特性。在本研究中，我们通过口服途径给予两种不同剂量的依维莫司，长期给药，证明其可抑制大鼠损伤颈动脉的内膜增生。
采用球囊扩张法建立大鼠颈动脉损伤模型。80 只大鼠随机分为假手术组（n = 20）、损伤组（n = 20）、低剂量依维莫司组（n = 20）和高剂量依维莫司组（n = 20）。低剂量依维莫司（1.5 mg/kg）在球囊损伤颈动脉前一天给予，随后通过灌胃每天给予 0.75 mg/kg，共 28 天。高剂量依维莫司（2.5 mg/kg）在球囊损伤颈动脉前一天给予，随后每天给予 1 mg/kg，共 28 天。通过逆转录-聚合酶链反应和 Western 印迹分析测定真核翻译起始因子 4E（eIF-4E）的表达和核糖体蛋白 S6 激酶 1（P70S6K）的磷酸化。
在损伤的颈动脉中，损伤后 4 周通常观察到内膜增生。依维莫司以剂量依赖性方式抑制球囊损伤后的内膜增生。同时，研究表明依维莫司降低了 P-P70S6K、eIF-4E、转化生长因子-β1 和增殖细胞核抗原（PCNA）的表达。
依维莫司显著抑制损伤颈动脉的内膜增生。这种作用取决于剂量，并与 P70S6K 磷酸化和 eIF-4E 表达水平的降低有关。
