Papanastasiou S, Estdale S E, Homer-Vanniasinkam S, Mathie R T
Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital, London. UK.
Br J Surg. 1999 Jul;86(7):916-22. doi: 10.1046/j.1365-2168.1999.01164.x.
Prolonged ischaemia followed by reperfusion (I/R) of skeletal muscle results in significant tissue injury. Ischaemic preconditioning (IPC), achieved by repeated brief periods of I/R before prolonged ischaemia or adenosine pretreatment, can prevent I/R injury in cardiac muscle. The aim of this study was to ascertain in a rodent model if damage to skeletal muscle due to global hindlimb tourniquet-induced I/R could be similarly attenuated.
Anaesthetized rats were randomized (n = 6-10 per group) to five groups: sham-operated controls; I/R (4 h of ischaemia, 2 h of reperfusion); IPC (three cycles of 10 min of ischaemia/10 min of reperfusion) alone; IPC immediately preceding I/R; or adenosine 1000 microg/kg immediately before I/R. At the end of reperfusion, biopsies were taken from the left gastrocnemius muscle for measurement of myeloperoxidase (MPO) and reduced glutathione (GSH). Before ischaemia and at the end of reperfusion, blood samples were taken for measurement of nitric oxide metabolites, tumour necrosis factor (TNF) alpha and macrophage inflammatory protein (MIP) 2.
IPC before I/R resulted in lower levels of MPO (P < 0.001) and TNF-alpha (P = 0.004), and higher levels of GSH (P < 0.001) and nitric oxide metabolites (P = 0.002) than I/R alone. Adenosine had effects comparable to IPC pretreatment (P < 0.001 for MPO, P = 0.002 for GSH, P = 0.02 for nitric oxide metabolites and P = 0.001 for TNF-alpha). There was no difference in the blood pressure or the MIP-2 concentration among the groups.
IPC or pretreatment with adenosine ameliorates the I/R injury of skeletal muscle.
骨骼肌长时间缺血后再灌注（I/R）会导致显著的组织损伤。缺血预处理（IPC）可通过在长时间缺血前反复进行短暂的I/R或腺苷预处理来实现，它能够预防心肌的I/R损伤。本研究的目的是在啮齿动物模型中确定，因后肢整体止血带诱导的I/R对骨骼肌造成的损伤是否能同样得到减轻。
将麻醉后的大鼠随机（每组n = 6 - 10）分为五组：假手术对照组；I/R组（缺血4小时，再灌注2小时）；单独的IPC组（三个10分钟缺血/10分钟再灌注周期）；I/R前立即进行IPC组；或在I/R前立即给予1000微克/千克腺苷组。再灌注结束时，从左腓肠肌取活检组织用于测定髓过氧化物酶（MPO）和还原型谷胱甘肽（GSH）。在缺血前和再灌注结束时，采集血样用于测定一氧化氮代谢产物、肿瘤坏死因子（TNF）α和巨噬细胞炎性蛋白（MIP）2。
与单独的I/R组相比，I/R前进行IPC可使MPO水平降低（P < 0.001）、TNF-α水平降低（P = 0.004），GSH水平升高（P < 0.001）以及一氧化氮代谢产物水平升高（P = 0.002）。腺苷的作用与IPC预处理相当（MPO为P < 0.001，GSH为P = 0.002，一氧化氮代谢产物为P = 0.02，TNF-α为P = 0.001）。各组间血压或MIP-2浓度无差异。
IPC或腺苷预处理可减轻骨骼肌的I/R损伤。
