Department of Anesthesia and Intensive Care, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China.
BMC Gastroenterol. 2011 Mar 31;11:31. doi: 10.1186/1471-230X-11-31.
Activation of heme oxygenase-1 (HO-1) has been proved to reduce damages to the liver in ischemia reperfusion injury. The objective of present study was to determine whether clinic relevant doses of isoflurane treatment could be sufficient to activate HO-1 inducing, which confers protective effect against hepatic ischemia-reperfusion injury.
The hepatic artery and portal vein to the left and the median liver lobes of forty male Sprague-Dawley rats were occluded for 60 minutes. Reperfusion was allowed for 4 hours before the animal subjects were sacrificed. Six groups (n = 12) were included in the study. A negative control group received sham operation and positive control group a standard ischemia-reperfusion regimen. The third group was pretreated with isoflurane prior to the ischemia-reperfusion. The fourth group received an HO-1 inhibitor zinc protoporphyrin (Znpp) prior to the isoflurane pretreatment and the ischemia-reperfusion. The fifth group received Znpp alone before ischemia-reperfusion procedure, and the sixth group was administrated with a HO-1 inducer hemin prior to IR. HO-1 in the liver was measured using an enzymatic activity assay, a Western blot analysis, as well as immunohistochemical method. Extent of liver damage was estimated by determination of the serum transaminases, liver lipid peroxidation and hepatic histology. Infiltration of the liver by neutrophils was measured using a myeloperoxidase activity assay. TNFα mRNA in the liver was measured using RT-PCR.
Isoflurane pretreatment significantly attenuated the hepatic injuries and inflammatory responses caused by the ischemia reperfusion. Selectively inhibiting HO-1 with ZnPP completed blocked the protective effects of isoflurane. Inducing HO-1 with hemin alone produced protective effects similar in magnitude to that of isoflurane.
Clinic relevant doses of isoflurane attenuate ischemia reperfusion injury in rats by increasing the HO-1 expression and activity.
血红素加氧酶-1（HO-1）的激活已被证明可减轻肝缺血再灌注损伤中的损伤。本研究的目的是确定临床相关剂量的异氟烷治疗是否足以激活 HO-1 诱导，从而对肝缺血再灌注损伤具有保护作用。
阻断 40 只雄性 Sprague-Dawley 大鼠的肝左动脉和门静脉以及中肝叶 60 分钟。在动物处死前允许再灌注 4 小时。本研究包括 6 个组（n = 12）。阴性对照组接受假手术，阳性对照组接受标准缺血再灌注方案。第三组在缺血再灌注前用异氟烷预处理。第四组在异氟烷预处理和缺血再灌注前给予 HO-1 抑制剂锌原卟啉（Znpp）。第五组在缺血再灌注前单独给予 Znpp，第六组在 IR 前给予 HO-1 诱导剂血红素。用酶活性测定、Western blot 分析和免疫组织化学方法测定肝内 HO-1。通过测定血清转氨酶、肝脂质过氧化和肝组织学来评估肝损伤程度。通过髓过氧化物酶活性测定法测量肝内中性粒细胞浸润。使用 RT-PCR 测定肝组织 TNFαmRNA。
异氟烷预处理显著减轻了缺血再灌注引起的肝损伤和炎症反应。用 ZnPP 选择性抑制 HO-1 完全阻断了异氟烷的保护作用。单独用血红素诱导 HO-1 产生的保护作用与异氟烷相似。
临床相关剂量的异氟烷通过增加 HO-1 的表达和活性来减轻大鼠的缺血再灌注损伤。
