Saidi Reza F, Chang Jennifer, Verb Steve, Brooks Steve, Nalbantoglu Ilke, Adsay Volkan, Jacobs Michael J
Department of Surgery, Providence Hospital and Medical Centers, Southfield, MI, USA.
Am J Surg. 2007 Mar;193(3):345-7; discussion 347-8. doi: 10.1016/j.amjsurg.2006.09.017.
Liver ischemia-reperfusion (I-R) injury is a well-known cause of morbidity and mortality following liver surgery and transplantation. Further investigation is warranted to identify measures that reduce the untoward sequelae of liver ischemia.
Male Sprague-Dawley rats (wild-type) and Zucker rats (with hepatic steatosis) were subjected to 75 minutes of 70% hepatic ischemia and 3 hours of reperfusion. The ischemic periods were based on protocols of either continuous clamping (CC) or ischemic preconditioning (IP). Prior to ischemia induction, rats were pretreated with intravenous methylprednisolone (MP; 2 mg/kg) or normal saline. Warm I-R injury was evaluated using serum levels of aspartate aminotransferase (AST), serum interleukin-6 (IL-6), and hematoxylin and eosin staining.
Histology, serum IL-6, and AST release revealed that MP treatment provided significant protection as compared with ischemic controls (both CC and IP groups) only in the normal, not steatotic, livers. The inflammatory response was considerably reduced in MP groups with normal livers but not in steatotic livers. In general, the IP groups showed decreased I-R injury compared to the CC group. However, MP was able to further reduce I-R injury only in normal, not steatotic, livers.
MP attenuated the postischemic and inflammatory response in the normal, and not steatotic, livers. MP pretreatment might be effective in reducing warm I-R injury to livers without steatosis. The mechanism of I-R-related hepatocellular damage in steatotic liver is different than in normal liver.
肝缺血再灌注（I-R）损伤是肝手术和移植后发病率和死亡率的一个众所周知的原因。有必要进一步研究以确定减少肝缺血不良后果的措施。
将雄性Sprague-Dawley大鼠（野生型）和Zucker大鼠（有肝脂肪变性）进行70%肝缺血75分钟及再灌注3小时。缺血期基于持续夹闭（CC）或缺血预处理（IP）方案。在诱导缺血前，大鼠经静脉给予甲泼尼龙（MP；2mg/kg）或生理盐水预处理。通过测定血清天冬氨酸转氨酶（AST）水平、血清白细胞介素-6（IL-6）水平及苏木精-伊红染色来评估热缺血再灌注损伤。
组织学、血清IL-6及AST释放显示，与缺血对照组（CC组和IP组）相比，MP治疗仅在正常而非脂肪变性的肝脏中提供了显著的保护作用。正常肝脏的MP组炎症反应明显减轻，但脂肪变性肝脏的MP组则不然。总体而言，与CC组相比，IP组的缺血再灌注损伤有所减轻。然而，MP仅在正常而非脂肪变性的肝脏中能够进一步减轻缺血再灌注损伤。
MP减轻了正常而非脂肪变性肝脏的缺血后及炎症反应。MP预处理可能对减轻无脂肪变性肝脏的热缺血再灌注损伤有效。脂肪变性肝脏中与缺血再灌注相关的肝细胞损伤机制与正常肝脏不同。
