Centro de Investigaciones Cardiovasculares ¨Dr Horacio E. Cingolani¨, CCT-CONICET, Universidad Nacional de La Plata, La Plata, Argentina.
Centro de Investigaciones Cardiovasculares ¨Dr Horacio E. Cingolani¨, CCT-CONICET, Universidad Nacional de La Plata, La Plata, Argentina.
Cardiovasc Pathol. 2018 Mar-Apr;33:19-26. doi: 10.1016/j.carpath.2017.12.003. Epub 2017 Dec 28.
The response to ischemia/reperfusion and the effects of ischemic post-conditioning (IPC) are sex-dependent, but the mechanisms have not been clarified. Male (M) and female (F) rat hearts isolated and perfused using the Langendorff technique were subject to 30 min of global ischemia (GI) and 60 min reperfusion (R). In IPC hearts, three cycles of 30-sec GI/30-sec R were applied at the beginning of R. Infarct size and myocardial function were assessed. Superoxide production, antioxidant systems, and expressions of phosphorylated forms of serine/threonine kinase (Akt), glycogen synthase kinase 3β (GSK-3β), protein kinase C ε (PKCε), endothelial nitric oxide synthase (eNOS), and apoptosis were measured. In the basal state, superoxide production and apoptosis were lower, and antioxidant systems and phospho-kinase expressions were higher in F rather than in M hearts. After ischemia-reperfusion, infarct size was less in F hearts, and post-ischemic recovery of myocardial function was higher in F rather than in M hearts. Superoxide production, phospho-kinase activity, phospho-eNOS, and apoptosis increased in both sexes while antioxidants decreased in both sexes. After IPC, infarct size, superoxide production, and apoptosis decreased and phospho-eNOS increased in F and M hearts but phospho-kinase expressions and post-ischemic recovery of myocardial function improved only in M hearts. These results show that Akt/GSK-3β/PKCε/eNOS-dependent pathways-mediated superoxide production and apoptosis appear as important factors involved in the observed gender differences.
缺血/再灌注的反应和缺血后处理（IPC）的效果是有性别依赖性的，但机制尚未阐明。使用 Langendorff 技术分离和灌注雄性（M）和雌性（F）大鼠心脏，进行 30 分钟的整体缺血（GI）和 60 分钟的再灌注（R）。在 IPC 心脏中，在 R 开始时应用三个 30 秒 GI/30 秒 R 的循环。评估梗塞面积和心肌功能。测量超氧化物的产生、抗氧化系统以及丝氨酸/苏氨酸激酶（Akt）、糖原合酶激酶 3β（GSK-3β）、蛋白激酶 C ε（PKCε）、内皮型一氧化氮合酶（eNOS）和凋亡的磷酸化形式的表达。在基础状态下，F 型心脏中超氧化物的产生和凋亡较低，而抗氧化系统和磷酸激酶的表达较高。在缺血再灌注后，F 型心脏的梗塞面积较小，而 F 型心脏的心肌功能在缺血后恢复较高。超氧化物的产生、磷酸激酶活性、磷酸化 eNOS 和凋亡在两性中均增加，而抗氧化剂在两性中均减少。IPC 后，F 和 M 心脏的梗塞面积、超氧化物的产生和凋亡减少，磷酸化 eNOS 增加，但仅在 M 心脏中磷酸激酶的表达和心肌功能的缺血后恢复得到改善。这些结果表明 Akt/GSK-3β/PKCε/eNOS 依赖性途径介导的超氧化物的产生和凋亡似乎是观察到的性别差异的重要因素。
