Ko J S, Gwak M S, Kim G S, Shin Y H, Ryu S, Kim J-S, Kim S J, Kim S T
Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
Transplant Proc. 2013 Jun;45(5):1704-7. doi: 10.1016/j.transproceed.2012.08.026.
Apoptosis is a central mechanism of ischemic-reperfusion injury (IRI) to the liver. Among the methods to reduce IRI, ischemic preconditioning (IP) has been shown to confer protection. Therefore, the aim of this study was to determine if IP conferred protection against hepatic IRI under isoflurane anesthesia in rats and to investigate underlying protective mechanisms.
Twenty-three rats weighing 270 to 300 grams were randomly divided into three groups: (1) the sham operated group (n = 5); (2) the non-IP group (n = 9; 45 minutes of hepatic ischemia followed by 2 hours of reperfusion); and (3) the IP group (n = 9); IP induced by 10 minutes of hepatic ischemia followed by 15 minutes of reperfusion before 45 minutes of prolonged hepatic ischemia). Anesthesia was maintained with isoflurane (1.5%). We compared the degrees of hepatic injury and expressions of B cell lymphoma 2 (Bcl-2) and caspase 3 and 8 mRNAs.
The IP group showed significantly lower levels of aspartate transaminase and alanine transaminase as well as reduced histological grades of hepatocyte injury compared with the non-IP group at 2 hours after reperfusion. At the corresponding time, the Bcl-2 mRNA level was 2-fold higher in the IP group. Caspase 3 mRNA levels were highest in the non-IP group significantly compared with the sham cohort. Similarly, caspase 8 mRNA levels were highest in the Non_IP group albeit not significancely.
IP protected against hepatic IRI under isoflurane anesthesia in rats. The mechanism of protection appeared to involve upregulation of Bcl-2 expression resulting in inhibited apoptosis.
细胞凋亡是肝脏缺血再灌注损伤（IRI）的核心机制。在减轻IRI的方法中，缺血预处理（IP）已被证明具有保护作用。因此，本研究的目的是确定IP在异氟烷麻醉下对大鼠肝脏IRI是否具有保护作用，并探讨其潜在的保护机制。
23只体重270至300克的大鼠随机分为三组：（1）假手术组（n = 5）；（2）非IP组（n = 9；肝脏缺血45分钟后再灌注2小时）；（3）IP组（n = 9；在延长的肝脏缺血45分钟前，先进行10分钟肝脏缺血再灌注15分钟诱导IP）。用异氟烷（1.5%）维持麻醉。我们比较了肝损伤程度以及B细胞淋巴瘤2（Bcl-2）、半胱天冬酶3和8 mRNA的表达。
再灌注2小时后，与非IP组相比，IP组天冬氨酸转氨酶和丙氨酸转氨酶水平显著降低，肝细胞损伤的组织学分级也降低。在相应时间，IP组Bcl-2 mRNA水平高2倍。与假手术组相比，非IP组半胱天冬酶3 mRNA水平显著最高。同样，非IP组半胱天冬酶8 mRNA水平最高，尽管差异不显著。
IP在异氟烷麻醉下对大鼠肝脏IRI具有保护作用。保护机制似乎涉及Bcl-2表达上调，从而抑制细胞凋亡。
