Department of Anesthesiology, First Affiliated Hospital, China Medical University, Liaoning, People's Republic of China.
J Surg Res. 2012 Nov;178(1):96-104. doi: 10.1016/j.jss.2012.02.021. Epub 2012 Mar 30.
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.
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 GSK-3β, Akt, and ERK1/2 were measured using Western blotting.
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-3β 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-3β Ser(9), Akt Ser(473), and ERK1/2 in NDRs, which were blocked in DRs.
The cardioprotection induced by sevoflurane postconditioning is abolished by diabetes. This might be due to the impairment of phosphorylation of GSK-3β and its upstream signaling pathways of phosphatidylinositol-3-kinase/Akt and ERK1/2 in the presence of diabetes.
我们测量了七氟醚后处理在链脲佐菌素诱导的糖尿病大鼠（DRs）中提供的心脏保护作用，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。
DRs 和非糖尿病大鼠（NDRs）接受 30 分钟的冠状动脉闭塞，随后进行 120 分钟的再灌注。再灌注的前 5 分钟，通过吸入 1 最小肺泡浓度七氟醚进行后处理。通过三苯基四唑氯化物染色确定梗死面积。使用 Western blot 测量 GSK-3β、Akt 和 ERK1/2 的表达。
在 NDRs 中，七氟醚后处理可将梗死面积从 53.4%±7.6%显著降低至 34.9%±5.6%（P<0.01）。然而，在 DRs 中，这种抗梗死作用完全被消除，因为在七氟醚处理和未处理的 DRs 之间观察到相似的梗死面积（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，可在 NDRs（SB216763 处理和未处理的 NDRs 分别为 37.8%±3.9%和 53.4%±7.6%；P<0.01）和 DRs（SB216763 处理和未处理的 DRs 分别为 38.8%±3.2%和 49.3%±8.6%；P<0.05）中诱导等效的梗死保护作用。七氟醚后处理可显著增强 NDRs 中 GSK-3β Ser(9)、Akt Ser(473)和 ERK1/2 的磷酸化，而在 DRs 中这种磷酸化被阻断。
糖尿病可消除七氟醚后处理诱导的心脏保护作用。这可能是由于在糖尿病存在的情况下，GSK-3β 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所致。
