Grad S, Ertel W, Keel M, Infanger M, Vonderschmitt D J, Maly F E
Institut für Klinische Chemie, Universitätsspital, Zürich, Switzerland.
Clin Chem Lab Med. 1998 Jun;36(6):379-83. doi: 10.1515/CCLM.1998.064.
Angiogenesis is a key component of the repair mechanisms triggered by tissue injury. Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis, as it acts directly and specifically on endothelial cells. VEGF produced locally in regenerating tissue may spill over into the systemic circulation, and measuring levels of circulating VEGF may allow monitoring of angiogenesis. To determine whether circulating VEGF is increased after severe injury, we measured concentrations of VEGF in serial serum samples of 23 mechanical burn patients, 55 patients with multiple trauma and 56 healthy normal controls, using a newly established ELISA assay. In burn patients, serum VEGF was increased on day 1 (369.4 +/- 88.0 pg/ml) and on day 3 (452.0 +/- 65.3 pg/ml), reached highest levels on day 14 (1809.5 +/- 239.7 pg/ml) and was still elevated on day 21 post-burn (1339.8 +/- 208.7 pg/ml) (mean +/- SEM, p < 0.01), when compared with healthy controls (82.2 +/- 10.8 pg/ml (mean +/- SEM)). Likewise, in trauma patients, serum VEGF showed a trend towards elevated values on the day of admission (186.9 +/- 43.9 pg/ml) and on day 3 after injury (193.2 +/- 62.1 pg/ml). Thereafter, serum VEGF increased further (day 7,507.0 +/- 114.7 pg/ml), peaked on day 14 (742.4 +/- 151.8 pg/ml) and was still elevated on day 21 after injury (693.1 +/- 218.6 pg/ml (mean +/- SEM, p < 0.01)). No significant correlation was observed between peak serum VEGF and initial severity of mechanical (Injury Severity Score) or burn injury (percentage of body surface burned). However, in both burn and trauma patients, the subgroup of patients with uncomplicated healing showed significantly higher increases of serum VEGF than the subgroup who developed severe complications during the post-traumatic course, such as sepsis, adult respiratory distress syndrome or multiple organ failure (p < 0.05). Thus, markedly enhanced levels of serum VEGF are present one to three weeks after trauma or burn injury. Further, occurrence of severe complications during the post-traumatic period is associated with lesser increases of serum VEGF.
血管生成是组织损伤触发的修复机制的关键组成部分。血管内皮生长因子(VEGF)是血管生成的重要介质,因为它直接且特异性地作用于内皮细胞。在再生组织中局部产生的VEGF可能会溢出到体循环中,测量循环VEGF水平可能有助于监测血管生成。为了确定严重损伤后循环VEGF是否升高,我们使用新建立的ELISA测定法,测量了23名机械烧伤患者、55名多发伤患者和56名健康正常对照者的系列血清样本中VEGF的浓度。在烧伤患者中,血清VEGF在第1天(369.4±88.0 pg/ml)和第3天(452.0±65.3 pg/ml)升高,在第14天达到最高水平(1809.5±239.7 pg/ml),并且在烧伤后第21天仍升高(1339.8±208.7 pg/ml)(平均值±标准误,p<0.01),与健康对照者(82.2±10.8 pg/ml(平均值±标准误))相比。同样,在创伤患者中,血清VEGF在入院当天(186.9±43.9 pg/ml)和受伤后第3天(193.2±62.1 pg/ml)呈现升高趋势。此后,血清VEGF进一步升高(第7天,507.0±114.7 pg/ml),在第14天达到峰值(742.4±151.8 pg/ml),并且在受伤后第21天仍升高(693.1±218.6 pg/ml(平均值±标准误,p<0.01))。在血清VEGF峰值与机械损伤(损伤严重度评分)或烧伤损伤(烧伤体表面积百分比)的初始严重程度之间未观察到显著相关性。然而,在烧伤和创伤患者中,愈合顺利的患者亚组血清VEGF的升高明显高于创伤后病程中发生严重并发症(如败血症、成人呼吸窘迫综合征或多器官功能衰竭)的患者亚组(p<0.05)。因此,创伤或烧伤损伤后1至3周血清VEGF水平明显升高。此外,创伤后期间发生严重并发症与血清VEGF升高幅度较小有关。