Phosphorylation of GSK-3β and reduction of apoptosis as targets of troxerutin effect on reperfusion injury of diabetic myocardium
Phosphorylation of GSK-3β and reduction of apoptosis as targets of troxerutin effect on reperfusion injury of diabetic myocardium
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DOI：
10.1016/j.ejphar.2015.08.056
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发表时间：
2015-10-15
影响因子：
5
通讯作者：
Mohammadi, Mustafa
中科院分区：
文献类型：
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作者：
Mokhtari, Behnaz;Badalzadeh, Reza;Mohammadi, Mustafa
糖尿病与缺血性心脏病有多种相互作用。曲克芦丁是一种黄酮类化合物，在心血管药物中具有良好的药理作用。本研究旨在探讨曲克芦丁对正常和糖尿病大鼠心肌缺血再灌注损伤后GSK-3β蛋白磷酸化和细胞凋亡的影响。雄性Wistar大鼠36只，体重250~300g，随机分为4组：健康组、糖尿病组、健康曲克芦丁组和糖尿病曲克芦丁组。单次注射链脲佐菌素(50 mg/kg；ip)诱发糖尿病，糖尿病病程持续10周。造模6周后，曲克芦丁治疗组大鼠口服曲克芦丁150 mg/kg/d，连续4周。将大鼠的心脏移植到朗宁多夫装置，然后进行30min的区域缺血，然后再灌流45min。采用ELISA法测定心肌肌钙蛋白I(CTnI)水平，Western blotting法检测心肌组织总GSK-3β和磷酸化GSK-3β水平，TUNEL法检测组织细胞凋亡率。与相应的对照组相比，曲克芦丁显著降低了健康组和糖尿病组的cTnI水平(P<；0.05)。此外，曲克芦丁显著增加糖尿病组和对照组GSK-3β的磷酸化水平和磷酸化/总形式的比率(P<；0.05)。对照组和糖尿病组给予曲克芦丁后，组织细胞凋亡率和细胞凋亡指数也显著降低(P<；0.05)。提示曲克芦丁通过抑制GSK-3β活性，进而减少细胞凋亡，对再灌流损伤有明显的心肌保护作用。(C)由爱思唯尔出版的2015年。
Diabetes has various interactions with ischemic heart diseases. Troxerutin, a flavonoid, owns outstanding pharmacological potentials in cardiovascular medicine. The purpose of this study was to investigate the effects of troxerutin on phosphorylation of GSK-3 beta protein and apoptosis induced by myocardial ischemia-reperfusion injury in healthy and diabetic hearts. Male Wistar rats (n=36, 250-300 g) were randomly divided into four groups: healthy, diabetic, healthy-troxerutin and diabetic-troxerutin. Diabetes was induced by a single injection of streptozotocin (50 mg/kg; ip) and the diabetic period was lasted for ten weeks. Six weeks after induction of diabetes, troxerutin-treated groups received 150 mg/kg/day troxerutin by oral gavage for 4 weeks. The rats' hearts were transferred to the Langendorff apparatus and then subjected to 30 min regional ischemia followed by 45 min reperfusion. Supernatants of the left ventricle were used to measure the levels of cardiac troponin-I (cTnI) by ELISA, total and phosphorylated form of GSK-3 beta by western blotting and tissue apoptosis by TUNEL assay. Troxerutin administration significantly decreased the cTnI levels in healthy and diabetic groups, as compared to the corresponding controls (P < 0.05). In addition, troxerutin significantly increased the level of phosphorylated form and the ratio of phosphorylated to total form of GsK-3 beta in diabetic and control groups (P < 0.05). Tissue apoptosis level and apoptotic index also showed a significant decrease after administration of troxerutin in control and diabetic groups (P < 0.05). The findings indicated that the attenuation of GSK-3 beta activity and subsequent reduction of apoptosis by troxerutin play significant roles in its cardioprotection on reperfusion injuries. (C) 2015 Published by Elsevier B.V.