Gregory C R, Huang X, Pratt R E, Dzau V J, Shorthouse R, Billingham M E, Morris R E
Department of Cardiothoracic Surgery, Stanford University School of Medicine, California 94305-5247.
Transplantation. 1995 Mar 15;59(5):655-61. doi: 10.1097/00007890-199503150-00002.
Rapamycin (RPM) and mycophenolic acid (MPA) inhibit immune responses by antagonizing IL-stimulated lymphocyte activation. These 2 drugs, used alone or preferably in combination, also significantly reduced the response of vascular cells to balloon-catheter arterial injury in rats. When rats were treated for 2 weeks with both drugs starting the day of injury, intimal thickening was significantly reduced (P < 0.001) 14 days after injury; however, by 44 days after injury, intimal thickening had progressed to the extent measured in arteries of untreated control rats. When RPM and MPA were administered for 3 days before and 13 days after injury, arterial intimal thickening was significantly (P = 0.024) reduced and endothelium had regrown in vessels analyzed 44 days after injury. Compared with initiation of treatment on the day of injury, starting the administration of RPM plus MPA before injury appears to limit the activation of cells or actions of factors responsible for the progression of intimal thickening that occurred after the administration of the drugs was terminated. RPM and MPA prevented the development of arterial intimal thickening in a model not dependent upon a rejection response. This direct antiproliferative action on smooth muscle cells by RPM and MPA, in vivo, may prevent the development of arterial intimal thickening associated with chronic rejection.
雷帕霉素（RPM）和霉酚酸（MPA）通过拮抗白细胞介素刺激的淋巴细胞活化来抑制免疫反应。这两种药物单独使用或优选联合使用时，还能显著降低大鼠血管细胞对球囊导管动脉损伤的反应。当大鼠在损伤当天开始用这两种药物治疗2周时，损伤后14天内膜增厚显著减少（P<0.001）；然而，损伤后44天时，内膜增厚已发展到未治疗对照大鼠动脉中测量到的程度。当在损伤前3天和损伤后13天给予RPM和MPA时，动脉内膜增厚显著（P = 0.024）减少，并且在损伤后44天分析的血管中内皮已再生。与在损伤当天开始治疗相比，在损伤前开始给予RPM加MPA似乎限制了在药物给药终止后发生的内膜增厚进展所负责的细胞活化或因子作用。RPM和MPA在一个不依赖于排斥反应的模型中阻止了动脉内膜增厚的发展。RPM和MPA在体内对平滑肌细胞的这种直接抗增殖作用可能会阻止与慢性排斥相关的动脉内膜增厚的发展。
