Gherardini G, Gürlek A, Milner S M, Matarasso A, Evans G R, Jernbeck J, Lundeberg T
Department of Surgery, Karolinska Hospital and Institutet, Stockholm, Sweden.
Neuropeptides. 1998 Jun;32(3):269-73. doi: 10.1016/s0143-4179(98)90047-6.
The effects of systemic administration of calcitonin gene-related peptide (CGRP) on survival and inflammation of experimental skin flaps subjected to prolonged arterial ischemia were studied. An island groin flap was elevated in the rat. The femoral artery was occluded for 8, 10, 12 or 14 h in four groups of 10 rats. In a group of 10 sham-operated control animals, the femoral artery was not occluded. After ischemia, blood flow was restored and flap survival evaluated at day 7. Following 12 h of ischemia, three flaps (30%) survived, compared with 100% survival of the control group. In the second part of the study the effects of CGRP on flap survival were assessed. Eighty flaps were rendered ischemic for 12 h, and received systemic CGRP (10(-7), 10(-8), 10(-9), 10(-10) M) or saline (control) at the end of the ischemia period. Administration of CGRP (10(-7) M) significantly increased the number of flaps surviving compared with the control. The effect of systemic pretreatment of the animals with the CGRP receptor antagonist CGRP8(-37), followed by CGRP (10(-7) M) treatment was also evaluated in 10 flaps. Flap survival in this group was 10%. In the third part of the study the anti-inflammatory effects of CGRP were evaluated. Forty rats were subjected to arterial ischemia for 12 h, and received systemic CGRP (10(-7) M), or saline at the end of the period of ischemia. The animals were sacrificed at 24 h and flap tissue samples were obtained. Myeloperoxidase (MPO) analysis was used as marker of neutrophil accumulation. CGRP (10(-7) M) significantly reduced the 24 h MPO accumulation in the flap, compared with saline treatment. A group of animals was pretreated with CGRP8(-37), followed by CGRP (10(-7) M), and a significant increase of MPO accumulation was seen, compared with the group treated only with CGRP. This study suggests that CGRP has a beneficial effect on survival of the rat ischemic groin flap, and diminishes the inflammatory response to the ischemic insult.
研究了全身给予降钙素基因相关肽（CGRP）对长时间动脉缺血的实验性皮瓣存活及炎症的影响。在大鼠身上掀起岛状腹股沟皮瓣。将10只大鼠分为四组，分别阻断股动脉8、10、12或14小时。另一组10只假手术对照动物未阻断股动脉。缺血后恢复血流，并在第7天评估皮瓣存活情况。缺血12小时后，三个皮瓣（30%）存活，而对照组皮瓣存活率为100%。在研究的第二部分，评估了CGRP对皮瓣存活的影响。80个皮瓣缺血12小时，在缺血期结束时给予全身CGRP（10^(-7)、10^(-8)、10^(-9)、10^(-10)M）或生理盐水（对照）。与对照组相比，给予CGRP（10^(-7)M）显著增加了存活皮瓣的数量。还对10个皮瓣评估了用CGRP受体拮抗剂CGRP8(-37)对动物进行全身预处理，然后给予CGRP（10^(-7)M）治疗的效果。该组皮瓣存活率为10%。在研究的第三部分，评估了CGRP的抗炎作用。40只大鼠动脉缺血12小时，在缺血期结束时给予全身CGRP（10^(-7)M）或生理盐水。在24小时处死动物并获取皮瓣组织样本。髓过氧化物酶（MPO）分析用作中性粒细胞聚集的标志物。与生理盐水治疗相比，CGRP（10^(-7)M）显著降低了皮瓣中24小时MPO的聚集。一组动物先用CGRP8(-37)预处理，然后给予CGRP（10^(-7)M），与仅用CGRP治疗的组相比，可见MPO聚集显著增加。该研究表明，CGRP对大鼠缺血性腹股沟皮瓣的存活有有益作用，并减轻了对缺血损伤的炎症反应。
