Glycogen synthase kinase 3 inhibition protects the heart from acute ischemia-reperfusion injury via inhibition of inflammation and apoptosis
Glycogen synthase kinase 3 inhibition protects the heart from acute ischemia-reperfusion injury via inhibition of inflammation and apoptosis
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DOI：
10.1097/fjc.0b013e318186a84d
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发表时间：
2008-09-01
影响因子：
3
通讯作者：
Wang, Hai-Chang
中科院分区：
文献类型：
--
作者：
Gao, Hao-Kao;Yin, Zhong;Wang, Hai-Chang
糖原合酶激酶 (GSK)-3 β 抑制剂在多种炎症性疾病中发挥所有抗炎作用。最近的研究表明，GSK-3 β 抑制剂可预防心肌缺血再灌注损伤。然而，确切的机制仍不清楚。我们的目的是研究缺血再灌注诱导的炎症和细胞凋亡在 GSK-3 β 抑制剂 4-benzyl-2-methyl-1, 2, 4-thiadiazolidine-3, 5-dione (TDZD-8) 心脏保护中的作用。麻醉的 Sprague-Dawley 大鼠接受所有开胸手术，包括 30 分钟的心肌缺血和 6 小时的再灌注，再灌注时给予或不给予 TDZD-8。 TDZD-8 使心肌梗塞面积减少近 43%（与心肌缺血再灌注组相比，P < 0.05），并减弱髓过氧化物酶活性（21.80 +/- 1.07 U/100 mg 组织。与心肌缺血再灌注组相比，P < 0.05）。 TDZD-8 给药显着抑制核因子 kappa B (NF-kappa B) 和 p38 MAPK 激活（与心肌缺血再灌注组相比，P < 0.05）以及心肌源性细胞因子肿瘤坏死因子-α（TNF-α，107.40 +/- 7.34 pg/mg 蛋白与心肌缺血再灌注组相比，P < 0.05）和白细胞介素 6 的浓度（IL-6，29.28 +/- 6.3 pg/mg 蛋白质与心肌缺血再灌注组相比，P < 0.05）。与心肌缺血再灌注组相比，TDZD-8治疗还抑制了心肌细胞凋亡（12 +/- 1%，vs. 22 +/- 2%，P < 0.05）。因此，阻断这种蛋白激酶活性可能是治疗这种疾病的一种新方法。其特征是炎症和细胞凋亡。
Glycogen synthase kinase (GSK)-3 beta inhibitors play all anti-inflammatory role in several inflammatory diseases. Recent studies have demonstrated that GSK-3 beta inhibitors protect against myocardial ischemia-reperfusion injury. However, the precise mechanisms remain unclear. We aimed to investigate the roles of inflammation and apoptosis induced by ischemia-reperfusion in the cardioprotection by GSK-3 beta inhibitor 4-benzyl-2-methyl-1, 2, 4-thiadiazolidine-3, 5-dione (TDZD-8). Anaesthetized Sprague-Dawley rats underwent all open-chest procedure involving 30 min of myocardial ischemia and 6 h of reperfusion with or without TDZD-8 given at reperfusion. TDZD-8 reduced myocardial infarct size by nearly 43%, (P < 0.05 vs. myocardial ischemia-reperfusion) and attenuated myeloperoxidase activity (21.80 +/- 1.07 U/100 mg tissue. vs. myocardial ischemia-reperfusion group, P < 0.05). Administration of TDZD-8 significantly suppressed nuclear factor kappa B (NF-kappa B) and p38 MAPK activation (P < 0.05 vs. myocardial ischemia-reperfusion) and the concentrations of the myocardial-derived cytokines tumor necrosis factor-alpha (TNF-alpha, 107.40 +/- 7.34 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05) and interleukin-6 (IL-6, 29.28 +/- 6.3 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05). Treatment with TDZD-8 also inhibited myocardial cell apoptosis compared with the myocardial ischemia-reperfusion group (12 +/- 1%, vs. 22 +/- 2%, P < 0.05). Therefore, blocking this protein kinase activity may be a novel approach to the treatment of this condition. which is characterized by inflammation and apoptosis.