Motomura N, Lou H, Maurice P, Foegh M L
Department of Surgery, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
Transplantation. 1997 Apr 15;63(7):932-6. doi: 10.1097/00007890-199704150-00004.
We demonstrate here, for the first time, the mitogenic effect of insulin-like growth factor-I (IGF-I) on the development of transplant arteriosclerosis in a rat orthotopic aorta allotransplantation model (Brown Norway to Lewis). 125I-IGF-I uptake by the abdominal aorta of male Brown Norway rats occurred within 30 min. Consequently, we exposed the donor abdominal aorta to 0, 200, or 500 ng/ml IGF-I at 37 degrees C for 30 min ex vivo (n=7 per group), before transplantation. Fourteen days after transplantation, intimal thickening of the allografts in each of the three groups was 0.18+/-0.02 (IGF-I at 0 ng/ml), 0.23+/-0.03 (IGF-I at 200 ng/ml), and 0.30+/-0.03 (IGF-I at 500 ng/ml), respectively (mean+/-SEM, P<0.005 for 500 ng/ml vs. 0 ng/ml). [3H]thymidine incorporation (cpm/microg protein) in the transplanted grafts at 7 days after transplantation (n=4 per group) was 40.6+/-7.6, 78.5+/-12.3, and 66.9+/-10.1, respectively (P<0.01 for 200 ng/ml vs. 0 ng/ml). [3H]thymidine incorporation in the native thoracic aorta of the recipient was 23.4+/-4.4. We conclude that acceleration of allograft myointimal proliferation and intimal thickening was induced directly by IGF-I.
我们在此首次证明，在大鼠原位主动脉同种异体移植模型（从布朗挪威大鼠到刘易斯大鼠）中，胰岛素样生长因子-I（IGF-I）对移植性动脉硬化的发展具有促有丝分裂作用。雄性布朗挪威大鼠腹主动脉对125I-IGF-I的摄取在30分钟内发生。因此，在移植前，我们将供体腹主动脉在37℃下离体暴露于0、200或500 ng/ml的IGF-I中30分钟（每组n = 7）。移植后14天，三组中每组同种异体移植物的内膜增厚分别为0.18±0.02（IGF-I为0 ng/ml）、0.23±0.03（IGF-I为200 ng/ml）和0.30±0.03（IGF-I为500 ng/ml）（平均值±标准误，500 ng/ml与0 ng/ml相比，P<0.005）。移植后7天，移植移植物中[3H]胸腺嘧啶核苷掺入量（cpm/μg蛋白质）（每组n = 4）分别为40.6±7.6、78.5±12.3和66.9±10.1（200 ng/ml与0 ng/ml相比，P<0.01）。受体天然胸主动脉中[3H]胸腺嘧啶核苷掺入量为23.4±4.4。我们得出结论，IGF-I直接诱导同种异体移植物肌内膜增殖和内膜增厚加速。
