自体原位肝移植术后早期胃氧化损伤及其与NF-E2相关因子2的关系

Patterns of Gastric Oxidative Damage and NF-E2-related Factor 2 Expression Alterations in SD Rats Subjected to Autologous Orthotopic Liver Transplantation

【目的】探讨SD大鼠自体原位肝移植后16 h内胃病理学变化特点,胃黏膜氧化损伤及NF-E2相关因子2(Nrf2)表达的变化。【方法】将24只SPF级SD大鼠随机均分为假手术组(Sham,n=6)、自体原位肝移植再灌注后4 h组(R4h)、自体原位肝移植再灌注后8 h组(R8h)和16 h组(R16h)。假手术组在麻醉后只进行开腹和血管的分离,不进行肝脏的阻断和灌注;其余各自体原位肝移植组则进行自体肝移植手术,观察胃组织病理学变化特点、羟自由基(·OH)、丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)及Nrf2蛋白表达的变化。【结果】自体原位肝移植引起了各组大鼠明显的胃黏膜损害,其中R4h组损伤最严重。与假手术组相比,自体原位肝移植后4 h和8 h胃黏膜的·OH及MDA水平均明显升高,伴随SOD、CAT活性的明显降低。Nrf2蛋白在自体原位肝移植再灌注后4 h表达下调,在8 h和1 6 h逐渐恢复至假手术组水平。相关分析显示,胃黏膜损伤评分与·OH和MDA含量呈正相关,与SOD和CAT活性呈负相关(P<0.05);Nrf2蛋白表达含量与胃黏膜损伤评分、·OH含量和MDA含量呈负相关,与CAT活性呈正相关(P<0.05)。【结论】大鼠自体原位肝移植引起胃损伤,胃损伤与修复与氧化和抗氧化能力变化一致;胃黏膜Nrf2表达增强可能有利于胃的自我修复。

[ Objective ] To investigate the dynamical changes of gastric pathology, oxidative damage and NF-E2-related factor 2 （Nrf2） expression after autologous orthotopic liver transplantation （AOLT）. [ Method ] Twenty-four Sprague-Dawley rats were randomly divided into four groups： Sham group, and R4h, 8 h and 16 h groups which were subjected to AOLT. Gastric specimens were collected to assay histopathological changes, levels of hydroxyl radical （-OH）, malondialdehyde （MDA）, superoxide dismutase （SOD） and catalase （CAT）, and Nrf2 expression. [Results] AOLT resulted in severe gastric injury in every AOLT group, and most dramatic in group R4h. Accompanied with significant decreases in the activity of SOD and CAT, the levels of ＂OH and MDA increased markedly, at 4 h and 8 h after AOLT, which indicated oxidative damage in gastric tissues. The expressions of Nrf2 in gastric tissues decreases significantly at 4h after AOLT, and then restored gradually at 8 h and 16 h after AOLT. The correlation analysis showed that there were positive correlations between gastric mucosal lesion and the content of ~ OH and MDA, and there were negative correlations between gastric mucosal lesion and the activity of SOD and CAT （P 〈 0.05）. However the correlations between the expressions of Nrf2 and gastric mucosal lesion, the content of ~ OH and MDA were negative correlations, and there was positive correlation between the expressions of Nrf2 and the activity of CAT （P 〈 0.05）. [ Conclusion ] AOLT could resulted in severe gastric injury. The damage and restoration of gastric tissue was according with the changes of oxidation and antioxidant capacity. Up-regulation of Nrf2 expression might be beneficial to the self-healing of gastric tissue.