Xu Si-Qi, Li Yuan-Hai, Hu Sheng-Hong, Chen Ke, Dong Liu-Yi
Department of Anesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China.
World J Gastroenterol. 2008 Dec 7;14(45):6936-42. doi: 10.3748/wjg.14.6936.
To investigate the effects and possible mechanisms of Wy14643 on hepatic ischemia-reperfusion (I/R) injury in rats.
Thirty male Sprague-Dawley rats weighing 220-280 g were randomly divided into five experimental groups: sham group (G1, n=6): a sham operation was performed (except for liver I/R); I/R-untreated group (G2, n=6): rats underwent liver ischemia for 90 min followed by reperfusion for 4 h; and I/R+Wy14643 groups (G3, G4, G5; n=6): after the same surgical procedure as in group 2, animals were pretreated with Wy14643 at the dose of 1, 5 and 10 mg/kg 1 h before ischemia, respectively. Hepatic ischemia-reperfusion (I/R) was induced by clamping blood supply to the left lateral and median lobes of the liver for 90 min, and atraumatic clamp was removed for 4 h reperfusion. Blood samples and liver tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase (ALT), aspartate aminotransferase (AST), myeloperoxidase (MPO), serum interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), as well as activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the hepatic tissue homogenate.
Hepatic I/R induced a significant increase in the serum levels of ALT, AST, TNF-alpha, IL-1beta and MPO, as well as the levels of ALT, AST and MDA in the liver tissue homogenate, which were reduced by pretreatment with Wy14643 at the dose of 1, 5 and 10 mg/kg, respectively. The activity of SOD in the liver tissue homogenate was decreased after hepatic I/R, which was enhanced by Wy14643 pretreatment. In addition, serum and liver tissue homogenate ALT and AST in the Wy14643 10 mg/kg group were lower than in the Wy14643 1 mg/kg and 5 mg/kg groups, respectively.
Wy14643 pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of anti-oxidant and inhibition inflammation response.
探讨Wy14643对大鼠肝脏缺血再灌注（I/R）损伤的影响及其可能机制。
将30只体重220 - 280 g的雄性Sprague-Dawley大鼠随机分为五个实验组：假手术组（G1，n = 6）：进行假手术（除肝脏I/R外）；I/R未处理组（G2，n = 6）：大鼠肝脏缺血90分钟，随后再灌注4小时；I/R + Wy14643组（G3、G4、G5；n = 6）：在与第2组相同的手术操作后，动物在缺血前1小时分别用1、5和10 mg/kg剂量的Wy14643进行预处理。通过夹闭肝脏左外叶和中叶的血液供应90分钟诱导肝脏缺血再灌注（I/R），然后移除无创伤夹进行4小时再灌注。在再灌注结束时采集血样和肝组织，以评估血清和肝组织匀浆中的氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、髓过氧化物酶（MPO）、血清白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α），以及肝组织匀浆中超氧化物歧化酶（SOD）的活性和丙二醛（MDA）的含量。
肝脏I/R导致血清中ALT、AST、TNF-α、IL-1β和MPO水平显著升高，以及肝组织匀浆中ALT、AST和MDA水平升高，而分别用1、5和10 mg/kg剂量的Wy14643预处理可降低这些水平。肝脏I/R后肝组织匀浆中SOD的活性降低，Wy14643预处理可增强其活性。此外，Wy14643 10 mg/kg组血清和肝组织匀浆中的ALT和AST分别低于Wy14643 1 mg/kg和5 mg/kg组。
Wy14643预处理对大鼠肝脏I/R损伤具有显著的保护作用。其保护作用可能与增强抗氧化和抑制炎症反应有关。
