罗格列酮对大鼠肝缺血再灌注损伤的保护作用  

Protective effects of rosiglitazone on hepatic ischemia reperfusion injury in rats

作　　者：陈季松[1] 刘海威[1] 张先林[1] CHEN Jisong;LIU Haiwei;ZHANG Xianlin(Department of General Surgery,Affiliated Renhe Hospital of China Three Gorges University,Yichang Hubai 443001,China)

机构地区：[1]三峡大学附属仁和医院普外科,湖北宜昌443001

出　　处：《中南大学学报（医学版）》2018年第7期732-737,共6页Journal of Central South University ：Medical Science

摘　　要：目的:探讨罗格列酮(rosiglitazone,RGZ)对肝缺血再灌注损伤(hepatic ischemia reperfusion injury,HIRI)的保护作用及其相关机制。方法:用无创血管夹夹闭左、中叶肝蒂构建70%HIRI大鼠模型。30只Sprague-Dawley大鼠随机均分为假手术组、HIRI组和RGZ组,每组10只。再灌注2 h后,检测血清中谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、乳酸脱氢酶(lactate dehydrogenase,LDH)表达水平,以及肝丙二醛(malondialdehyde,MDA)的含量和过氧化氢酶(content and catalase,CAT)、谷胱甘肽过氧化物酶(glutathione peroxidase,GPx)、超氧化物歧化酶(superoxide dismutase,SOD)的活性;HE染色检测肝病理形态;Western印迹检测肝过氧化物酶体增殖物激活受体-γ(peroxisome proliferators-activated receptorγ,PPAR-γ)、磷酸化修饰的PPAR-γ(p-PPAR-γ)、核因子相关因子2(nuclear factor related factor 2,Nrf-2)、抗氧化反应元件(antioxidant response element,ARE)、血红素氧化酶1(heme oxygenase 1,HO-1)、还原型辅酶/醌氧化还原酶-1(quinone oxidoreductase-1,NQO-1)表达量。结果:与HIRI组相比,RGZ组ALT,AST,LDH和MDA表达水平均明显降低(均P<0.05),而p-PPAR-γ,Nrf-2,ARE,HO-1和NQO-1表达水平,以及CAT,GPX和SOD活性均明显增高(均P<0.05),此外,肝组织肿胀和坏死以及病理损伤均明显减轻(均P<0.05),而PPAR-γ表达水平差异无统计学意义(P>0.05)。结论:PPAR-γ激动剂RGZ能减轻肝HIRI,其作用途径可能与激活Nrf2/ARE信号途径而增强机体抗氧化能力有关。Objective： To explore the protective effect ofrosiglitazone （RGZ） on hepatic ischemia reperfusion injury （HIRI） and the underlying mechanisms. Methods： A rat model of ischemia-reperfusion injury was established by clamping the left and middle lobe of liver with noninvasive vascular clamp. A total of 30 Sprague-Dawley rats were randomly divided into a sham group, an HIRI group, and a RGZ group （10 rats in each group）. Two hours after reperfusion, serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities, lactate dehydrogenase （LDH） level, malondialdehyde （MDA） content and catalase （CAT）, glutathione peroxidase （GPx） and superoxide dismutase （SOD） activities were examined. HE staining was used to observe liver pathological morphology, The liver peroxisome proliferators-activated receptor 3＇ （PPAR-3r）, P＇PPAR-γ, nuclear factor related factor 2 （Nrf-2）, antioxidant response element （ARE）, heme oxygenase 1 （HO-1） and quinone oxidoreductase-1 （NQ,O- 1） were detected by Western blot. Results： Compared with the HIRI group, the levels of ALT, AST, LDH and MDA in the RGZ group were significantly decreased （all P〈0.05）, while the levels of Nrf-2, ARE, HO-1 and NQO-1 in the RGZ group were significantly increased. The hepatic swelling, necrosis and pathological damage were decreased （all P〈0.05）. In addition, there was no difference in the level of PPAR-γ between the 2 groups （P〉0.05）. Conclusion： PPAR-γ agonist RGZ can attenuate HIRI, which may be related to activating Nrf2/ ARE signaling pathway and enhancement of antioxidant ability.

关 键 词：罗格列酮 肝缺血再灌注损伤 氧化应激 

分 类 号：R575[医药卫生—消化系统]