Harmon D, Lan W, Shorten G
Cork University Hospital, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland.
Eur J Anaesthesiol. 2004 Dec;21(12):973-9. doi: 10.1017/s0265021504000365.
An acute inflammatory response associated with cerebral ischaemia-reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery.
Human neutrophil CD11 b/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1beta supernatant concentrations in response to in vitro hypoxia-reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL(-1)). Adhesion molecule expression was quantified using flow cytometry and IL-1beta concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student-Newman-Keuls test as appropriate.
Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170+/-46% vs. 91+/-27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170+/-46% vs. 129+/-40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased endothelial cell ICAM-1 expression (155+/-3.7 vs. 43+/-21 mean channel fluorescence, P = 0.0003) and IL-1beta supernatant concentrations compared to normoxia (3.4+/-0.4 vs. 2.6+/-0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation produced greater upregulation of ICAM- 1 expression [(155+/-3.3 vs. 116+/-0.7) (P = 0.001)] and IL-1beta supernatant concentrations [(3.4+/-0.3 vs. 2.6+/-0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3).
Hypoxia-reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1beta concentrations is decreased by aprotinin at clinically relevant concentrations.
与脑缺血再灌注相关的急性炎症反应会促使脑损伤的发展。抑肽酶对接受心脏手术的患者具有潜在的神经保护作用，尽管其机制尚不明晰。
在有或没有抑肽酶（1600 KIU mL⁻¹）存在的情况下，研究体外缺氧复氧时人中性粒细胞CD11b/CD18、内皮细胞细胞间黏附分子-1（ICAM-1）的表达以及内皮白细胞介素（IL）-1β上清液浓度。使用流式细胞术对黏附分子表达进行定量，通过酶联免疫吸附测定法测定IL-1β浓度。数据采用方差分析及适当的事后Student-Newman-Keuls检验进行分析。
与常氧相比，暴露于60分钟缺氧状态下，中性粒细胞CD11b表达增加（荧光强度百分比相对于0时刻，分别为170±46% 对91±27%，P = 0.001）（n = 8）。与用抑肽酶处理的中性粒细胞相比，缺氧（60分钟）使对照组中CD11b表达上调幅度更大[（170±46% 对129±40%）（P = 0.04）]（n = 8）。与常氧相比，缺氧复氧增加了内皮细胞ICAM-1表达（平均通道荧光分别为155±3.7对43±21，P = 0.0003）以及IL-1β上清液浓度（分别为3.4±0.4对2.6±0.2，P = 0.02）（n = 3）。与用抑肽酶处理的内皮细胞制剂相比，缺氧复氧使对照组中ICAM-1表达上调幅度更大[（155±3.3对116±0.7）（P = 0.001）]以及IL-1β上清液浓度上调幅度更大[（3.4±0.3对2.6±0.1）（P = 0.01）]（n = 3）。
在临床相关浓度下，抑肽酶可降低缺氧复氧诱导的中性粒细胞CD11b、内皮细胞ICAM-1表达及IL-1β浓度的上调。
