Claytor R Brannon, Aranson Nathan J, Ignotz Ronald A, Lalikos Janice F, Dunn Raymond M
Division of Plastic and Reconstructive Surgery, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA.
J Reconstr Microsurg. 2007 Feb;23(2):93-8. doi: 10.1055/s-2007-970189.
Ischemic preconditioning has been shown to improve survival of cutaneous flaps. The authors examined the effect of remote ischemic preconditioning (RIPC) on phosphorylation of p38 MAP kinase and related the results to flap survival. Female Wistar rats had 8 x 12-cm abdominal adipocutaneous flaps raised on the medial branch of the superficial epigastric artery. Controls (Group 1) had the flap elevated and the pedicle clamped for 3 hr, then closed with a sheet of plastic between the flap and abdominal wall. Group 2 animals had RIPC by tourniquet on the contralateral hind limb before the flap was dissected. Group 3 animals mimicked Group 2 and also had an infusion of the nitric oxide blocker, N-nitro-L-arginine methyl ester (L-NAME) 5 min prior to the RIPC. Group 4 had the flap elevated prior to the RIPC. All groups except Group 1 had 10 min of RIPC with 30 min of reperfusion, then 3 hr of ischemia. Tissue samples were taken at the distal margins of the flaps before preconditioning and 30 min after preconditioning for detection of p38 MAP kinase and phosphorylated p38 MAP kinase (pp38 MAP kinase). Group 2 flaps (RIPC before flap elevation) exhibited better flap tissue survival and had well-defined phosphorylation of p38 MAP kinase 30 min post RIPC, when compared to the other groups. Pre-infusion with the nitric oxide blocker (Group 3) before RIPC blocked the survival advantage conferred by preconditioning and diminished the phosphorylation of p38 MAP kinase. Tissue from all groups showed very little phosphorylation of p38 MAP kinase following 3 hr of ischemia. Thus, increased tissue survival is correlated with elevated levels of p38 MAP kinase phosphorylation following RIPC. This effect is inhibited by blockade of nitric oxide. Modulation of the p38 MAP kinase pathway may represent a protection pathway for ischemic preconditioning.
缺血预处理已被证明可提高皮瓣的存活率。作者研究了远程缺血预处理（RIPC）对p38丝裂原活化蛋白激酶（MAP激酶）磷酸化的影响，并将结果与皮瓣存活率相关联。雌性Wistar大鼠在腹壁浅动脉内侧支上掀起8×12厘米的腹部脂肪皮瓣。对照组（第1组）掀起皮瓣并将蒂夹闭3小时，然后在皮瓣与腹壁之间用一块塑料片闭合。第2组动物在解剖皮瓣前通过对侧后肢使用止血带进行RIPC。第3组动物模仿第2组，并且在RIPC前5分钟还输注一氧化氮阻滞剂N-硝基-L-精氨酸甲酯（L-NAME）。第4组在RIPC前掀起皮瓣。除第1组外，所有组均进行10分钟的RIPC并再灌注30分钟，然后缺血3小时。在预处理前和预处理后30分钟从皮瓣的远端边缘采集组织样本，以检测p38 MAP激酶和磷酸化p38 MAP激酶（pp38 MAP激酶）。与其他组相比，第2组皮瓣（皮瓣掀起前进行RIPC）表现出更好的皮瓣组织存活率，并且在RIPC后30分钟p38 MAP激酶有明确的磷酸化。在RIPC前预先输注一氧化氮阻滞剂（第3组）可阻断预处理赋予的存活优势，并减少p38 MAP激酶的磷酸化。所有组的组织在缺血3小时后p38 MAP激酶的磷酸化都很少。因此，组织存活率的提高与RIPC后p38 MAP激酶磷酸化水平的升高相关。这种作用被一氧化氮的阻断所抑制。p38 MAP激酶途径的调节可能代表缺血预处理的一种保护途径。
