Boston, Mass.; and Chicago, Ill. From the Divisions of Plastic and Reconstructive Surgery and Vascular and Endovascular Surgery, Massachusetts General Hospital, Harvard Medical School; and the Departments of Surgery, Medicine, Organismal Biology, and Anatomy, Committee on Molecular Medicine, University of Chicago.
Plast Reconstr Surg. 2010 Jun;125(6):1651-1660. doi: 10.1097/PRS.0b013e3181ccdbef.
Ischemia-reperfusion injury can activate pathways generating reactive oxygen species, which can injure cells by creating holes in the cell membranes. Copolymer surfactants such as poloxamer 188 are capable of sealing defects in cell membranes. The authors postulated that a single-dose administration of poloxamer 188 would decrease skeletal myocyte injury and mortality following ischemia-reperfusion injury.
Mice underwent normothermic hind-limb ischemia for 2 hours. Animals were treated with 150 microl of poloxamer 188 or dextran at three time points: (1) 10 minutes before ischemia; (2) 10 minutes before reperfusion; and (3) 2 or 4 hours after reperfusion. After 24 hours of reperfusion, tissues were analyzed for myocyte injury (histology) and metabolic dysfunction (muscle adenosine 5'-triphosphate). Additional groups of mice were followed for 7 days to assess mortality.
When poloxamer 188 treatment was administered 10 minutes before ischemia, injury was reduced by 84 percent, from 50 percent injury in the dextran group to 8 percent injury in the poloxamer 188 group (p < 0.001). When administered 10 minutes before reperfusion, poloxamer 188 animals demonstrated a 60 percent reduction in injury compared with dextran controls (12 percent versus 29 percent). Treatment at 2 hours, but not at 4 hours, postinjury prevented substantial myocyte injury. Preservation of muscle adenosine 5'-triphosphate paralleled the decrease in myocyte injury in poloxamer 188-treated animals. Poloxamer 188 treatment significantly reduced mortality following injury (10 minutes before, 75 percent versus 25 percent survival, p = 0.0077; 2 hours after, 50 percent versus 8 percent survival, p = 0.032).
Poloxamer 188 administered to animals decreased myocyte injury, preserved tissue adenosine 5'-triphosphate levels, and improved survival following hind-limb ischemia-reperfusion injury.
缺血再灌注损伤可激活生成活性氧的途径，这些活性氧可通过在细胞膜上形成孔来损伤细胞。共聚物表面活性剂如泊洛沙姆 188 能够封闭细胞膜上的缺陷。作者推测，单次给予泊洛沙姆 188 可减少缺血再灌注损伤后的骨骼肌肌细胞损伤和死亡率。
小鼠进行常温下肢缺血 2 小时。动物在三个时间点用 150μl 泊洛沙姆 188 或葡聚糖处理：（1）缺血前 10 分钟；（2）再灌注前 10 分钟；和（3）再灌注后 2 或 4 小时。再灌注 24 小时后，分析组织的肌细胞损伤（组织学）和代谢功能障碍（肌肉三磷酸腺苷）。对另外几组小鼠进行 7 天的随访以评估死亡率。
当在缺血前 10 分钟给予泊洛沙姆 188 治疗时，损伤减少了 84%，从葡聚糖组的 50%损伤减少到泊洛沙姆 188 组的 8%损伤（p<0.001）。当在再灌注前 10 分钟给予时，与葡聚糖对照组相比，泊洛沙姆 188 动物的损伤减少了 60%（12%对 29%）。在损伤后 2 小时给予，但不在 4 小时后给予，可预防严重的肌细胞损伤。在泊洛沙姆 188 治疗的动物中，肌肉三磷酸腺苷的保存与肌细胞损伤的减少平行。泊洛沙姆 188 治疗可显著降低损伤后的死亡率（缺血前 10 分钟，75%与 25%的存活率，p=0.0077；2 小时后，50%与 8%的存活率，p=0.032）。
给予动物泊洛沙姆 188 可减少肌细胞损伤，保存组织三磷酸腺苷水平，并改善下肢缺血再灌注损伤后的存活率。
