Yu Xiaofang, Chi Xinjin, Wu Shan, Jin Yi, Yao Hui, Wang Yiheng, Xia Zhengyuan, Cai Jun
Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China ; Department of Anesthesiology, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China.
Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
Oxid Med Cell Longev. 2016;2016:4675817. doi: 10.1155/2016/4675817. Epub 2015 Nov 22.
This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecific α2 receptor blocker) + high dose Dex (group B1), ARC239 (a specific α2B/c receptor blocker) + high dose Dex (group B2), and BRL-44408 (a specific α2A receptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (all P < 0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 through α2A receptor, increases the antioxidant levels, and attenuates renal injury during OALT.
本文旨在探讨在原位自体肝移植(OALT)期间,右美托咪定(Dex)预处理是否具有抗氧化和肾脏保护作用及其对核因子红细胞2相关因子2(Nrf2)激活的影响。将Sprague-Dawley大鼠随机分为假手术组(S组)、模型组(M组)、低剂量Dex组(D1组)、高剂量Dex组(D2组)、阿替美唑(一种非特异性α2受体阻滞剂)+高剂量Dex组(B1组)、ARC239(一种特异性α2B/c受体阻滞剂)+高剂量Dex组(B2组)和BRL-44408(一种特异性α2A受体阻滞剂)+高剂量Dex组(B3组)。然后在OALT术后8小时对肾脏进行组织病理学检查,并测量肾功能、肾脏Nrf2蛋白表达以及氧化剂和抗氧化剂水平。我们发现,Dex预处理可激活肾小球细胞中的Nrf2并上调抗氧化剂,但降低氧化剂水平(所有P<0.01,D2组与M组相比)。阿替美唑和BRL-44408可逆转这些保护作用,但ARC239不能。总之,Dex预处理通过α2A受体激活Nrf2,增加抗氧化剂水平,并减轻OALT期间的肾脏损伤。