The selective 5-LOX inhibitor 11-keto-β-boswellic acid protects against myocardial ischemia reperfusion injury in rats: involvement of redox and inflammatory cascades
The selective 5-LOX inhibitor 11-keto-β-boswellic acid protects against myocardial ischemia reperfusion injury in rats: involvement of redox and inflammatory cascades
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DOI：
10.1007/s00210-013-0885-9
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发表时间：
2013-09-01
影响因子：
3.6
通讯作者：
Nassar, Noha N.
中科院分区：
文献类型：
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作者：
Elshazly, Shimaa M.;Abd El Motteleb, Dalia M.;Nassar, Noha N.
心肌缺血诱导心脏5-脂氧合酶(LOX)易位和白三烯的产生。白三烯增加炎症反应，加重缺血再灌注损伤。本研究旨在探讨选择性5-LOX抑制剂11-酮-β-博斯威酸(11-keto-beta-Boshelic acid，11-Keto-BA)在三种不同剂量水平对在体大鼠心脏I/R损伤的保护作用。雄性Wistar大鼠60只，随机分为5组(n=12)：假手术组(GP1)，结扎冠状动脉左前降支45min，再灌注4h，作为I/R组。GPS3-5分别以250、500、1000 mg/kg剂量灌胃给予11-酮BA，连续灌胃7d后，心肌组织谷胱甘肽过氧化物酶活性及细胞内黏附分子环氧合酶-2，5-脂氧合酶、核因子-kappa-β、肿瘤坏死因子-α、核因子-2和血红素加氧酶-1基因表达显著增加，谷胱甘肽过氧化物酶活性降低。此外，免疫组织化学检查显示，所有患病大鼠心脏组织3-硝基酪氨酸和半胱氨酸天冬氨酸氨基转移酶-3均呈阳性反应，并形成DNA梯形带。3个剂量水平的11-酮BA具有剂量依赖性的心肌保护作用，表现为剂量依赖性地降低血清乳酸脱氢酶和心肌梗死面积，其机制与增强抗氧化能力和防止炎症级联有关。
Myocardial ischemia induces 5-lipoxygenase (LOX) translocation and leukotriene production in the heart. Leukotrienes increase inflammatory responses aggravating, thereby, ischemia-reperfusion (I/R) injury. This study aimed to investigate whether the selective 5-LOX inhibitor 11-keto-beta-boswellic acid (11-keto BA), in three different dose levels, exert a protective effect on myocardial I/R injury in an in vivo rat heart model. Sixty male Wister rats were used in this study and divided into five equal groups (n = 12): GP1, sham-operated receiving normal saline; Gp 2, rats were subjected to 45 min left anterior descending coronary artery ligation followed by 4 h reperfusion to serve as I/R group. Gps 3-5 received 11-keto BA in doses 250, 500, 1,000 mg/kg, respectively, via an oral gavage for 7 days then were exposed to I/R. I/R injury induced a significant elevation in myeloperoxidase activity and gene expression of intracellular adhesion molecules, cyclooxygenase-2, 5-lipooxygenasae, nuclear factor kappa-beta, tumor necrosis factor alpha, nuclear factor (erythroid-derived 2)-like 2, and hemeoxygenease-1 consequently with reduction in glutathione peroxidase in heart tissues. Furthermore, immunohistochemical examination of the heart tissues showed positive immuostaining for both 3-nitrotyrosine and caspase-3 with DNA-ladder formation in all diseased rats. 11-keto BA in three dose levels exerted dose dependent cardioprotective effect manifested by dose-dependent reduction in serum lactate dehydrogenase and infract size through mechanisms related to enhancement of antioxidant capacity and prevention of inflammatory cascades.