Ischemic preconditioning prevents postischemic P-selectin expression in the rat small intestine.
Ischemic preconditioning prevents postischemic P-selectin expression in the rat small intestine.
复制标题
缺血预处理可防止大鼠小肠缺血后 P-选择素的表达。
DOI：
10.1152/ajpheart.1999.277.6.h2476
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Korthuis,RJ
中科院分区：
文献类型：
--
作者：
Davis,JM;Gute,DC;Jones,S;Krsmanovic,A;Korthuis,RJ
缺血预适应 (IPC) 可防止长时间缺血和再灌注 (I/R) 的有害影响。由于白细胞浸润是产生小肠 I/R 诱导的微血管功能障碍所必需的，并且 P-选择素依赖性白细胞滚动是该过程中的必要步骤，因此我们假设 IPC 会减弱缺血后 P-选择素的表达。为了解决这个假设，使用双放射性标记单克隆抗体方法在非缺血（对照）大鼠空肠和仅经受 I/R（20 分钟缺血/60 分钟再灌注）或 IPC（5 分钟缺血/10 分钟再灌注）+ I/R 的大鼠空肠中评估 P-选择素表达。 I/R 与空肠 P-选择素表达增加七倍相关，这种效应被 IPC 完全消除。在预适应缺血期间将肠道暴露于腺苷脱氨酶或腺苷 A1 受体拮抗剂，而不是 A2 受体拮抗剂，或在长时间缺血期间暴露于选择性 PKC 拮抗剂，会阻止 IPC 限制 I/R 诱导的 P-选择素表达的有益作用。我们的数据表明，P-选择素表达是 IPC 中腺苷启动的、PKC 依赖性抗炎信号通路的新型下游效应靶标。
Ischemic preconditioning (IPC) prevents the deleterious effects of prolonged ischemia and reperfusion (I/R). Because leukocyte infiltration is required to produce the microvascular dysfunction induced by I/R in the small intestine, and P-selectin-dependent leukocyte rolling is a requisite step in this process, we hypothesized that IPC would attenuate postischemic P-selectin expression. To address this postulate, P-selectin expression was evaluated in nonischemic (control) rat jejunum and in rat jejunum subjected to I/R alone (20 min ischemia/60 min reperfusion), or IPC (5 min ischemia/10 min reperfusion) + I/R using a dual radiolabeled monoclonal antibody approach. I/R was associated with a sevenfold increase in jejunal P-selectin expression, an effect that was completely abolished by IPC. Exposing the bowel to adenosine deaminase or an adenosine A1, but not an A2, receptor antagonist during the period of preconditioning ischemia or to selective PKC antagonists during prolonged ischemia prevented the beneficial effect of IPC to limit I/R-induced P-selectin expression. Our data indicate that P-selectin expression is a novel downstream effector target of the adenosine-initiated, PKC-dependent, anti-inflammatory signaling pathway in IPC.