中文摘要：

目的研究孕烷X受体（pregnane X receptor,PXR）介导克霉唑抗大鼠肝缺血再灌注损伤作用及其机制。方法 SD大鼠随机分成4组,分别为假手术组、缺血再灌注组、克霉唑低剂量组和克霉唑高剂量组。以谷丙转氨酶（ALT）、谷草转氨酶（AST）、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性、丙二醛（MDA）含量及热休克蛋白70（HSP70）蛋白表达等为观察指标,用终浓度分别为25 mg/kg和50 mg/kg的克霉唑预处理大鼠5 d,5 h后观察其对肝缺血再灌注损伤的作用。结果 PXR特异性强诱导剂克霉唑,与假手术组比,能明显诱导CYP3A1基因表达,表现为ALT、AST和LDH显著降低（P〈0.05）,且呈剂量依赖性,SOD和GSH-Px活性分别升高,MDA显著降低,对抗氧自由基ROS损伤,上调HSP70表达（P〈0.05）,表现出强大的抗缺血再灌注损伤作用。结论克霉唑预具有较好抗肝缺血再灌注损伤的保护作用,其机制可能在PXR介导下,拮抗ROS损伤及内源性保护蛋白HSP70表达上调有关。

英文摘要：

Objective To investigate the possib reperfusion injury in rats using clotrimazole （CTZ）, were divided into 4 groups of 8 each ： sham-treated, le role of the pregnane X receptor （PXR） in hepatic ischemia- a strong PXR transactivator. Methods Male Sprague-Dawtey rats control, and CTZ-treated animals. The rats were pretreated with 25 mg/kg and 50 mg/kg CTZ for 5 d, respectively. Control and CTZ treated animals were subjected to 30 min of normothermic ischemia of the whole liver followed by 5 h of reperfusion, and the animals were then killed, and the liver was excised and blood samples were collected, the activities of ALT, AST, SOD and GSH-Px, MDA contents, LDH activity and heat shock proteins 70 （HSP70） protein expression were measured. Results Clotrimazole induced a significant increase in expression of the CYP3A1 gene, indicating PXR transactivation, whereas pretreatment with CTZ decreased LDH, ALT, AST activity and MDA contents, the activities of SOD and GSH-Px in a concentration dependent manner, and increased HSP70 protein expression. Conclusion Clotrimazole-mediated PXR transactivation protects the liver against ischemia reperfusion in rats. The mechanism is involved in inhibiting reactive oxygen species, and expression of HSP70 is up-regulated by induction of PXR.