Belkin M, LaMorte W L, Wright J G, Hobson R W
Department of Surgery, Boston University Medical Center, Mass.
J Vasc Surg. 1989 Jul;10(1):14-8; discussion 18-9. doi: 10.1067/mva.1989.vs0100014.
Neutrophilic leukocytes have been implicated as important mediators of ischemic myocardial injury. We investigated the role of neutrophils in skeletal muscle ischemia/reperfusion injury by using the rat hindlimb ischemia model. We rendered Wistar rats neutropenic by administering 750 rad of whole-body radiation (mean white blood cell count, 300 +/- 50/mm3; 3 days after radiation). In anesthetized rats (10 neutropenic and 10 control), 3 hours of ischemia were induced in one hindlimb by application of a tourniquet to the proximal thigh; the contralateral limb served as an internal, nonischemic control. After 1 hour of reperfusion the gastrocnemius and soleus muscles were excised bilaterally and evaluated for ischemic injury by means of a quantitative spectrophotometric assay of triphenyltetrazolium chloride (TTC) reduction. In control rats the reduction of TTC by ischemic muscle averaged 27.0% +/- 7.3% of that by nonischemic muscle; whereas in neutropenic rats the value for ischemic muscle was 65.4 +/- 11.6% (p less than 0.05). To determine if the contribution of the neutrophils to ischemic injury is due to oxygen-derived free radical formation, an additional 10 animals were infused with 5000 units of super-oxide dismutase and 10,000 units of catalase at the time reperfusion was restored. After treatment with free radical scavengers, TTC reduction by ischemic limbs was 25.5% +/- 7.0% of that by nonischemic limbs and did not differ from that in control animals (p greater than 0.05). The results show a protective effect of neutropenia and suggest a significant role of the white cell in the pathophysiology of ischemic skeletal muscle injury.
中性粒细胞被认为是缺血性心肌损伤的重要介质。我们通过使用大鼠后肢缺血模型研究了中性粒细胞在骨骼肌缺血/再灌注损伤中的作用。我们通过给予750拉德的全身辐射使Wistar大鼠中性粒细胞减少（辐射后3天，平均白细胞计数为300±50/mm³）。在麻醉的大鼠（10只中性粒细胞减少的大鼠和10只对照大鼠）中，通过在大腿近端应用止血带使一侧后肢缺血3小时；对侧肢体作为内部非缺血对照。再灌注1小时后，双侧切除腓肠肌和比目鱼肌，并通过定量分光光度法测定氯化三苯基四氮唑（TTC）还原率来评估缺血损伤。在对照大鼠中，缺血肌肉的TTC还原率平均为非缺血肌肉的27.0%±7.3%；而在中性粒细胞减少的大鼠中，缺血肌肉的值为65.4±11.6%（p<0.05）。为了确定中性粒细胞对缺血损伤的作用是否归因于氧衍生自由基的形成，在恢复再灌注时，向另外10只动物输注5000单位的超氧化物歧化酶和10000单位的过氧化氢酶。用自由基清除剂处理后，缺血肢体的TTC还原率为非缺血肢体的25.5%±7.0%，与对照动物无差异（p>0.05）。结果显示中性粒细胞减少具有保护作用，并提示白细胞在缺血性骨骼肌损伤的病理生理学中起重要作用。
