Diabetes abolishes the cardioprotection induced by sevoflurane postconditioning in the rat heart in vivo: Roles of glycogen synthase kinase-3β and its upstream pathways
Diabetes abolishes the cardioprotection induced by sevoflurane postconditioning in the rat heart in vivo: Roles of glycogen synthase kinase-3β and its upstream pathways
复制标题
DOI：
10.1016/j.jss.2012.02.021
复制
发表时间：
2012-11-01
影响因子：
2.2
通讯作者：
Ai, Chunyu
中科院分区：
文献类型：
--
作者：
Tai, Wenjun;Shi, Enyi;Ai, Chunyu
背景：我们测量了七氟醚后处理对链脲佐菌素诱导的糖尿病大鼠 (DR) 的心脏保护作用，并确定了糖原合酶激酶 (GSK)、磷脂酰肌醇-3-激酶/Akt 和细胞外信号调节激酶 (ERK1/2) 在该过程中的作用。方法：对 DR 和非糖尿病大鼠 (NDR) 进行 30 分钟的冠状动脉闭塞随后进行 120 分钟的再灌注。后处理是通过在再灌注前 5 分钟吸入 1 次最低肺泡浓度七氟烷来实现的。通过氯化三苯基四唑染色测定梗塞大小。使用蛋白质印迹法测量 GSK3 beta、Akt 和 ERK1/2 的表达。结果：在 NDR 中，七氟烷后处理后梗死面积从 53.4% +/- 7.6% 显着减小至 34.9% +/- 5.6%（P < 0.01）。这种抗梗塞作用在 DR 中完全消失，七氟烷治疗组和未治疗 DR 之间观察到的梗塞面积相似（分别为 49.3% +/- 8.6% 和 49.6% +/- 9.3%，P > 0.05）。在再灌注开始前注射SB216763直接抑制GSK-3β在两种NDR（经SB216763治疗和未治疗的NDR中分别为37.8%+/-3.9%和53.4%+/-7.6%；P<0.01）和DR（38.8%+/-3.2%和SB216763 治疗和未治疗的 DR 中分别为 49.3% +/- 8.6%（P < 0.05）。七氟烷后处理显着增强了NDR中GSK-3 beta Ser(9)、Akt Ser(473)和ERK1/2的磷酸化，而在DR中则被阻断。结论：七氟烷后处理诱导的心脏保护作用被糖尿病消除。这可能是由于糖尿病存在时 GSK-3 β 及其上游磷脂酰肌醇-3-激酶/Akt 和 ERK1/2 信号通路的磷酸化受损。 (C) 2012 Elsevier Inc. 保留所有权利。
Background: We measured the cardioprotection afforded by sevoflurane postconditioning in streptozotocin-induced diabetic rats (DRs) and determined the roles of glycogen synthase kinase (GSK), phosphatidylinositol-3-kinase/Akt, and extracellular signal-regulated kinase (ERK1/2) in such a procedure.Methods: DRs and nondiabetic rats (NDRs) were subjected to a 30-min coronary artery occlusion followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of 1 minimum alveolar concentration sevoflurane at the first 5 min of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. Expressions of GSK3 beta, Akt, and ERK1/2 were measured using Western blotting.Results: In NDRs, the infarct size was significantly decreased from 53.4% +/- 7.6% to 34.9% +/- 5.6% by sevoflurane postconditioning (P < 0.01). Such an anti-infarct effect was abolished completely in the DRs, as evidenced by a similar infarct size observed between the sevoflurane-treated and untreated DRs (49.3% +/- 8.6% and 49.6% +/- 9.3%, respectively, P > 0.05). Direct inhibition of GSK-3 beta by injection of SB216763 just before the start of reperfusion induced equivalent infarct-sparing effects in both NDRs (37.8% +/- 3.9% and 53.4% +/- 7.6% in SB216763-treated and untreated NDRs, respectively; P < 0.01) and DRs (38.8% +/- 3.2% and 49.3% +/- 8.6% in SB216763-treated and untreated DRs, respectively; P < 0.05). Sevoflurane postconditioning remarkably enhanced the phosphorylation of GSK-3 beta Ser(9), Akt Ser(473), and ERK1/2 in NDRs, which were blocked in DRs.Conclusions: The cardioprotection induced by sevoflurane postconditioning is abolished by diabetes. This might be due to the impairment of phosphorylation of GSK-3 beta and its upstream signaling pathways of phosphatidylinositol-3-kinase/Akt and ERK1/2 in the presence of diabetes. (C) 2012 Elsevier Inc. All rights reserved.