罗格列酮对大鼠肝缺血再灌注损伤的保护作用

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 receptor γ，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。

Protective effects of rosiglitazone on hepatic ischemia reperfusion injury in rats

Objective: To explore the protective eff ect of rosiglitazone (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). Twohours 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 γ (PPAR-γ), p-PPAR-γ, nuclear factor related factor 2 (Nrf-2), antioxidant response element (ARE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-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.