Altavilla D, Squadrito F, Ioculano M, Canale P, Campo G M, Zingarelli B, Caputi A P
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Eur J Pharmacol. 1994 Jan 3;270(1):45-51. doi: 10.1016/0926-6917(94)90079-5.
The role of E-selectin in the pathogenesis of an experimental model of myocardial ischemia-reperfusion injury was investigated. Pentobarbital anesthetized rats underwent left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham operated rats were used as controls (sham MI/R). Myocardial ischemia-reperfusion injury reduced survival rate (50%), caused severe myocardial damage (necrotic area/area-at-risk 69.8 +/- 5%; necrotic area/total area = 56 +/- 7.6%), increased serum creatine phosphokinase activity (sham MI/R = 33 +/- 3 U/ml; MI/R = 215 +/- 13 U/ml), and elevated myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation; sham MI/R = 0.11 +/- 0.02 U x 10(-3)/g tissue) in the area-at-risk (7.5 +/- 1.7 U x 10(-3)/g tissue) and in the necrotic area (7.8 +/- 2.2 U x 10(-3)/g tissue). Furthermore, MI/R rats had an increased pressure rate index, studied as a quantitative means for assessing myocardial oxygen demand. Administration of a hyperimmune serum containing antibodies against E-selectin significantly improved survival rate (80%), reduced myocardial injury (necrotic area/area-at-risk = 26.4 +/- 7%, P < 0.005; necrotic area/total area 19.1 +/- 2.8%, P < 0.005), lowered serum creatine phospokinase activity (85 +/- 5 U/ml, P < 0.001) and decreased myeloperoxidase activity in the area at risk (3.7 +/- 1.3 U x 10(-3)/g tissue, P < 0.001) and in the necrotic area (3.0 +/- 0.7 U x 10(-3)/g tissue). Finally, the administration of anti E-selectin antibodies improved the PRI in MI/R rats. The present data suggest that E-selectin in vivo plays a key role in the pathogenesis of myocardial ischemia/reperfusion injury.
研究了E-选择素在心肌缺血-再灌注损伤实验模型发病机制中的作用。戊巴比妥麻醉的大鼠进行左冠状动脉主干结扎（1小时），随后再灌注（1小时；MI/R）。假手术大鼠用作对照（假MI/R）。心肌缺血-再灌注损伤降低了存活率（50%），导致严重的心肌损伤（梗死面积/危险面积69.8±5%；梗死面积/总面积=56±7.6%），增加了血清肌酸磷酸激酶活性（假MI/R=33±3U/ml；MI/R=215±13U/ml），并提高了危险区域（7.5±1.7U×10⁻³/g组织）和坏死区域（7.8±2.2U×10⁻³/g组织）的髓过氧化物酶活性（作为白细胞黏附和聚集的指标进行研究；假MI/R=0.11±0.02U×10⁻³/g组织）。此外，MI/R大鼠的压力速率指数增加，该指数作为评估心肌需氧量的定量手段进行研究。给予含有抗E-选择素抗体的超免疫血清可显著提高存活率（80%），减少心肌损伤（梗死面积/危险面积=26.4±7%，P<0.005；梗死面积/总面积19.1±2.8%，P<0.005），降低血清肌酸磷酸激酶活性（85±5U/ml，P<0.001），并降低危险区域（3.7±1.3U×10⁻³/g组织，P<0.001）和坏死区域（3.0±0.7U×10⁻³/g组织）的髓过氧化物酶活性。最后，给予抗E-选择素抗体改善了MI/R大鼠的PRI。目前的数据表明，体内E-选择素在心肌缺血/再灌注损伤的发病机制中起关键作用。
