目的 探讨核因子E2相关因子2（nuclear factor erythroid 2-related factor 2，Nrf2）/抗氧化反应元件（antioxidant response element，ARE）信号通路在吗啡预处理减轻心力衰竭（heart failure，HF）大鼠心肌缺血再灌注损伤（myocardial ischemia-reperfusion injury，MIRI）中的作用机制。 方法 首先制作HF模型大鼠并将其随机分为sham组，模型组，MFC组，MOA组和OAD组，同时设立正常组；HF模型鼠予以结扎左冠状动脉前降支30 min，再灌注120 min构建为MIRI模型，其中MFC组术前经吗啡预处理，OAD组术前经Nrf2/ARE信号通路抑制剂预处理，MOA组术前经Nrf2/ARE信号通路抑制剂+吗啡预处理。TUNEL检测细胞凋亡率，Western blot检测Nrf2和HO-1表达。 结果 与正常组相比，模型组细胞凋亡率、Nrf2和HO-1表达升高；与模型组相比，MFC组细胞凋亡率降低，Nrf2和HO-1升高；与MFC组相比，MOA组细胞凋亡率升高，Nrf2和HO-1表达降低；与模型组相比，OAD组细胞凋亡率升高，Nrf2和HO-1表达降低；差异均具有统计学意义（P<0.05）。 结论 在HF导致的MIRI大鼠模型中，吗啡预处理能激活Nrf2/ARE通路，抑制细胞凋亡。
Abstract
Objective To investigate the role of the nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway in reduction of myocardial ischemia-reperfusion injury (MIRI) by morphine preconditioning in rats with heart failure induced by doxorubicin hydrochloride. Methods The HF model rats were randomly divided into the following 5 groups: a sham group, a model group, a MFC group, a MOA group and an OAD group. The normal group was set at the same time. The HF model rats were ligated at the anterior descending branch of the left coronary artery for 30 minutes and then were perfused for 120 minutes to construct the MIRI model. The MFC group rats were pretreated with morphine before operation. The OAD group rats were pretreated with Nrf2/ARE signaling pathway inhibitor before operation, the MOA group with Nrf2/ARE signaling pathway inhibitor plus morphine. TUNEL was used to detect the apoptosis rate. Western blot was used to detect the expressions of Nrf2 and HO-1. Results Compared with the normal group, the apoptosis rate and the expressions of Nrf2 and HO-1 in the model group significantly increased. Compared with the model group, the apoptosis rate of the MFC group significantly reduced, and the expressions of Nrf2 and HO-1 significantly increased. Compared with the MFC group, the apoptosis rate of the MOA group significantly increased, and the expressions of Nrf2 and HO-1 significantly reduced. Compared with the model group, the apoptosis rate of the OAD group significantly increased, and the expressions of Nrf2 and HO-1 significantly increased. There were statistical differences in the expressions of Nrf2, HO-1 and the apoptosis rate among the groups (P<0.05). Conclusions In the MIRI rat model induced by HF, morphine preconditioning can obviously activate the Nrf2/ARE pathway and inhibit cell apoptosis.
关键词
吗啡； 心力衰竭； 盐酸多柔比星；心肌缺血再灌注损伤； /
Nrf2/ARE信号通路
Key words
Heart failure; Doxorubicin hydrochloride; Myocardial ischemia-reperfusion injury /
Nrf2/ARE signaling pathway
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