血红素氧合酶-1介导匹伐他汀对大鼠肝脏缺血再灌注损伤的保护作用  

The protective effects of HO-1 induced by pitavastatin on hepatic inflammation and injury caused by ischemia reperfusion in rats

作　　者：侯英健[1] 于哲[2] 步玉辉[3] 韩艳梅[1] 

机构地区：[1]河北大学基础医学院,河北保定071002 [2]华北油田总医院,河北任丘062552 [3]河北大学临床医学院,河北保定071002

出　　处：《医学研究与教育》2013年第1期9-14,共6页Medical Research and Education

基　　金：国家自然科学基金(81200078);河北省高等学校科学技术研究项目(Q2012006);保定市科技攻关项目(11ZF087);河北大学学科建设项目(2012A1001)

摘　　要：目的研究匹伐他汀对大鼠肝脏缺血再灌注(IR)损伤的保护作用,并探讨其中机理。方法将雄性SD大鼠随机分为假手术组、IR组、他汀治疗组、他汀-ZnPP联合处理组。再灌注8 h后收集血液,分离肝组织。检测大鼠血清转氨酶以及肝组织髓过氧化物酶(MPO)水平,以实时定量PCR检测肝组织血红素氧合酶-1(HO-1)、细胞间粘附分子-1(ICAM-1)和诱导型一氧化氮合成酶(iNOS)的mRNA水平。结果 IR导致明显的炎症反应与肝组织损伤,与之相比匹伐他汀使ALT、AST以及MPO水平下降,ICAM-1和iNOS表达下调,NF-κB的磷酸化水平降低,肝组织损伤情况改善。而匹伐他汀组前述保护作用被HO抑制剂——锌原卟啉(ZnPP)所阻断,他汀预处理使HO-1表达显著增高。结论匹伐他汀通过上调HO-1表达,抑制炎症反应,在肝脏IR损伤中发挥保护作用。Objective To explore the underlying mechanisms and effects of pitavastatin on hepatic inflammation and injury induced by ischemia reperfusion（IR） in rats. Methods Male Sprague-Dawley rats were randomly divided into 4 groups： a sham-operation group, an ischemia,reperfusion （IR） group, a pitavastatin therapy group and a pitavastatin- ZnPP group. Eight hours post reperfusion, blood was collected and hepatic tissue was isolated. Then, we detected the levels of ALT and AST in the serum as well as myeloperoxidase （MPO） in the liver. Additionally, realtime- PCR was performed to assay HO-1, iNOS and ICAM-1 expression. Results IR induced dramatic hepatic inflammation and injury in rats. Compared with the IR group, pitavastatin treatment lowered the levels of ALT, AST and MPO, suppressed the expression of two pro-inflammatory genes such as iNOS and ICAM-I, and improved hepatic lesions. Nevertheless, an HO inhibitor, ZnPP, reversed the protective effects of pitavastatin on IR injury. Furthermore, HO-1 expression was induced by IR and further promoted by statin treatment. Conclusion Mediated by promoted HO-1 expression, pitavastatin plays a protective role for hepatic inflammation and IR injury in rats.

关 键 词：缺血再灌注 炎症 血红素氧合酶-1 匹伐他汀 

分 类 号：R575[医药卫生—消化系统]