Dunne J B, Piratvisuth T, Williams R, Tredger J M
Institute of Liver Studies, King's College Hospital, London, England.
Transplantation. 1997 Feb 27;63(4):500-6. doi: 10.1097/00007890-199702270-00003.
Triple therapy with S-adenosylmethionine (SAM) (given to the donor animal, included in University of Wisconsin solution [UW], and added to the reperfusing medium) has been shown to reduce the sequential cold and warm ischemia/reperfusion injuries characteristic of the liver transplantation procedure. To clarify the actions of SAM during different stages of ischemia/ reperfusion, we have compared its benefit in five dosage regimens, using perfused rat livers after sequential periods of 24 hr cold and 20 min rewarming ischemia. When added only to UW, the presence of SAM throughout ischemia improved hepatic blood flow by 26% after 15 min of reperfusion versus no treatment (2.32+/-0.18 vs. 1.84+/-0.11 ml/min/g liver, P<0.05). SAM also improved blood flow by 23% during the 3-hr perfusion overall (P<0.05). Oxygen consumption and the release of purine nucleoside phosphorylase (PNP) were decreased (both P<0.05). When added to both UW and the perfusate, SAM additionally increased bile production at 15 min (7.14+/-1.21 vs. 2.31+/-0.74 mg/h/g liver, P<0.01). By pretreating the liver donor with SAM in vivo, and including it in the preservation and reperfusing media, it was possible to prolong and amplify the benefits on blood flow (P<0.001) and bile production (P<0.05) and to sustain glucose uptake (P<0.01). An acute exposure to SAM, when used in saline to flush UW from the graft before reperfusion, increased blood flow at 15 min (by 68%) and over a 3-hr period (both P<0.001), but no indices of metabolic activity were improved. Oxygen consumption and PNP release were both decreased (P<0.05). When added to the perfusate (present throughout reperfusion), SAM increased blood flow at 15 min (58%) and over a 3-hr period (P<0.01 in both cases). Net glucose uptake was increased (P<0.05), whereas oxygen consumption (P<0.001) and PNP release fell (P<0.05). Actions of SAM achieved acutely and over the intermediate- and long-term all seem to underlie its benefits in reducing ischemia/reperfusion injuries.
已证明，采用S-腺苷甲硫氨酸（SAM）进行三联疗法（给予供体动物，包含在威斯康星大学溶液[UW]中，并添加到再灌注培养基中）可减少肝移植手术特有的序贯性冷缺血和温缺血/再灌注损伤。为阐明SAM在缺血/再灌注不同阶段的作用，我们比较了其在五种给药方案中的益处，采用了在经历24小时冷缺血和20分钟复温缺血后进行灌注的大鼠肝脏。仅添加到UW中时，在整个缺血过程中存在SAM可使再灌注15分钟后肝血流量比未治疗时提高26%（2.32±0.18对1.84±0.11 ml/min/g肝脏，P<0.05）。在整个3小时灌注期间，SAM也使血流量提高了23%（P<0.05）。氧消耗和嘌呤核苷磷酸化酶（PNP）的释放均降低（均P<0.05）。当同时添加到UW和灌注液中时，SAM在15分钟时还增加了胆汁生成（7.14±1.21对2.31±0.74 mg/h/g肝脏，P<0.01）。通过在体内对肝脏供体进行SAM预处理，并将其包含在保存和再灌注培养基中，有可能延长并放大对血流量（P<0.001）和胆汁生成（P<0.05）的益处，并维持葡萄糖摄取（P<0.01）。在再灌注前用生理盐水冲洗移植物中的UW时急性暴露于SAM，可使15分钟时血流量增加（68%），并在3小时内增加（均P<0.001），但代谢活性指标未得到改善。氧消耗和PNP释放均降低（P<0.05）。当添加到灌注液中（在整个再灌注过程中存在）时，SAM使15分钟时血流量增加（58%），并在3小时内增加（两种情况均P<0.01）。净葡萄糖摄取增加（P<0.05），而氧消耗（P<0.001）和PNP释放下降（P<0.05）。SAM在急性、中期和长期所产生的作用似乎都是其减少缺血/再灌注损伤益处的基础。
