Department of Physiology II, Kanazawa Medical University, Ishikawa, Japan.
Department of Colorectal and Hernia Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
PLoS One. 2020 Nov 17;15(11):e0242026. doi: 10.1371/journal.pone.0242026. eCollection 2020.
Angiopoietin (Angpt)-2, a permeability-increasing growth factor, is involved in vascular leakage of sepsis and acute lung injury, and could be released from endothelium in response to anaphylaxis-related secretagogues such as histamine and leukotrienes, or cytokines. However, roles of Angpt-2 in the hyperpermeability during systemic anaphylaxis are not known. Thus, we determined plasma levels of Angpt-2 and cytokines and vascular permeability during anaphylactic hypotension in unanesthetized rats. Anaphylaxis was induced by an intravenous injection of ovalbumin antigen. Mean arterial blood pressure (MBP) was measured, and hematocrit (Hct) and plasma levels of Angpt-2 and cytokines were assessed for 24 h after antigen injection. Separately, vascular permeability was measured in various organs using the Evans blue dye method, and Angpt-2 mRNA expression in liver was measured. After antigen injection, MBP decreased to the nadir at 6 min, and returned to baseline at 45 min, and Hct peaked at 20 min and thereafter progressively declined, suggesting that vascular leak and hypotension occurred within 20 min. Plasma Angpt-2 levels began to increase significantly at 1 h after antigen, reaching the peak 2.7-fold baseline at 6 h with a return to baseline at 24 h. Detected cytokines of IL-1α, IL-1β, IL-6, IL-10, and TNF-α peaked 1 or 2 h after antigen. Angpt-2 mRNA increased at 2 h and showed an increasing tendency at 6 h. Vascular permeability in bronchus, trachea, intestines, mesentery and skeletal muscle was increased at 10 min but not at 6 h after antigen. In addition, we confirmed using anesthetized rat anaphylaxis models that plasma Angpt-2 levels increased at 1 h after antigen. In conclusion, plasma Angpt-2 is elevated presumably due to increased cytokines and enhanced gene transcription during anaphylaxis in anesthetized and unanesthetized rats.
血管生成素 (Angpt)-2 是一种增加血管通透性的生长因子，参与败血症和急性肺损伤的血管渗漏，并且可以作为过敏反应相关的分泌物（如组胺和白三烯）或细胞因子从内皮细胞中释放出来。然而，Angpt-2 在全身性过敏反应中的高通透性中的作用尚不清楚。因此，我们在未麻醉大鼠的过敏反应性低血压期间测定了 Angpt-2 和细胞因子的血浆水平和血管通透性。通过静脉注射卵清蛋白抗原诱导过敏反应。测量平均动脉血压 (MBP)，并在抗原注射后 24 小时评估血细胞比容 (Hct)和 Angpt-2 及细胞因子的血浆水平。另外，使用 Evans 蓝染料法测量各种器官的血管通透性，并测量肝脏中的 Angpt-2 mRNA 表达。抗原注射后，MBP 在 6 分钟时降至最低点，在 45 分钟时恢复到基线，Hct 在 20 分钟时达到峰值，此后逐渐下降，表明血管渗漏和低血压发生在 20 分钟内。抗原后 1 小时，血浆 Angpt-2 水平开始显著增加，在 6 小时时达到基线的 2.7 倍峰值，并在 24 小时时恢复到基线。检测到的细胞因子 IL-1α、IL-1β、IL-6、IL-10 和 TNF-α在抗原后 1 或 2 小时达到峰值。Angpt-2 mRNA 在 2 小时时增加，并在 6 小时时呈增加趋势。抗原后 10 分钟支气管、气管、肠道、肠系膜和骨骼肌的血管通透性增加，但在 6 小时时没有增加。另外，我们在麻醉大鼠过敏反应模型中证实，抗原后 1 小时血浆 Angpt-2 水平增加。总之，在麻醉和未麻醉大鼠的过敏反应中，血浆 Angpt-2 升高可能是由于细胞因子增加和基因转录增强所致。
