异氟烷预处理对大鼠肝窦内皮缺血再灌注损伤的影响  

Effects of isoflurane preconditioning on ischemia-reperfusion injury to liver sinusoidal endothelium in rats

作　　者：黄施伟[1] 李士通[1] 王莹恬[1] 王立中[1] 徐国辉[1] 庄心良[1] 

机构地区：[1]上海市第一人民医院麻醉科,200080

出　　处：《中华麻醉学杂志》2007年第4期347-351,共5页Chinese Journal of Anesthesiology

基　　金：上海市卫生局青年科研基金资助项目（034y06）

摘　　要：目的 研究异氟烷预处理对大鼠肝窦内皮常温缺血再灌注（I/R）损伤的影响,并探讨线粒体ATP敏感性钾通道（Mito-KATP）在其中的作用。方法 48只健康成年雄性SD大鼠,随机分为6组（n=8）。假手术组（S组）：进腹后仅分离韧带但不阻断血流;对照组（C组）：进腹后行部分肝脏缺血60min再灌注90min;异氟烷预处理组（Iso组）：吸入1．5%（1MAC）异氟烷30min,停止吸入10min后行I/R;5-HD＋Iso组：在吸入异氟烷前10min静脉注射5-羟葵酸（5-HD）10 mg/kg;二氮嗪组（Dia组）：I/R前10min静脉注射二氮嗪5mg/kg;5-HD＋Dia组：I/R前20min静脉注射5-HD 10mg/kg,10min后静脉注射二氮嗪5mg/kg。各组再灌注90min时测定血清谷丙转氨酶（ALT）的活性和透明质酸（HA）的浓度;以硝酸还原酶法检测肝组织一氧化氮（NO）含量,放免法检测内皮素（ET）含量;免疫组化法检测细胞间粘附分子-1（ICAM-1）的表达水平;光镜和电镜下观察肝组织病理学改变。结果 （1）与S组比较,C组血清ALT活性、HA浓度、肝组织ET含量和ICAM-1表达水平均升高,而肝组织NO含量降低（P＜0．05）。（2）异氟烷和二氮嗪预处理能抑制I/R引起的血清ALT活性及HA浓度、肝组织ET含量及ICAM-1表达水平的升高和肝组织NO含量的降低（P＜0．05）。（3）光镜和透射电镜检查提示Iso组和Dia组I/R所致的肝窦内皮细胞损伤减轻。（4）5-HD可完全阻断二氮嗪预处理对肝窦内皮的保护作用,但只能部分阻断异氟烷预处理对肝窦内皮的保护作用。结论 1．5%异氟烷预处理30min可减轻大鼠肝窦内皮缺血再灌注损伤,其部分机制通过开放Mito-KATP。Objective To investigate the effects of isoflurane preconditioning on warm ischemiareperfusion （I/R） injury to liver sinusoidal endothelium and the role mitochondrial ATP-sensitive K ^＋ channels play in the mechanism. Methods Male SD rats weighing 220-280 g were used in this study. The animals were anesthetized with intraperitoneal 1% pentobarbital 50 mg/kg. Right internal jugular vein and femoral artery were eannulated for fluid infusion and MAP and HR monitoring. Body temperature was maintained at 37.5-38.5℃ . Liver I/R was induced by clamping the middle and left hepatic artery and portal vein, resulting in 70 percent of liver isehemie. The animals were randomly divided into 6 groups （ n = 8 each） ： （1） sham operation group; （2） I/ R group; （3） Iso preconditioning group inhaled 1.5% isoflurane （1 MAC） for 30 min followed by 10 min washout before I/R; （4） 5-HD ＋ Iso preconditioning group received 5-hydroxy-deeanoate （5-HD） 10 mg/kg given intravenously 10 min before isoflurane preconditioning; （5） Dia ＋ I/R group received diazoxide 5 mg/kg intravenously 10 min before I/R and （6） 5-HD ＋ Dia group received 5-HD 10 mg/kg and diazoxide 5 mg/kg at 10 min interval 20 min before I/R. Isehemia was maintained for 60 min. At 90 min reperfusion blood samples and tissue samples from liver were obtained for （1） determination of serum hyaluronie acid （HA） concentration and alanine aminotransferase （ALT） activity; （2） examination of ultrastrueture of liver with electron microscope and （3） determination of NO and endothelin （ET） contents and ICAM-1 expression in liver. Results （1） Serum ALT activity and HA concentration and liver ET content and ICAM-1 expression were significantly higher while liver NO content was significantly lower in I/R group than in sham operation group （ P 〈 0.05 ） . （ 2 ） Isoflurane and diazoxide preconditioning significantly attenuated the increase in serum ALT activity and HA concentration and liver ET content and

关 键 词：异氟醚 缺血预处理 再灌注损伤 钾通道 内皮 血管 肝 

分 类 号：R686[医药卫生—骨科学]