Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Eur J Pharmacol. 2015 Oct 15;765:316-21. doi: 10.1016/j.ejphar.2015.08.056. Epub 2015 Sep 1.
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-3β 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-3β 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-3β 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-3β activity and subsequent reduction of apoptosis by troxerutin play significant roles in its cardioprotection on reperfusion injuries.
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,在心血管医学中具有突出的药理潜力。本研究旨在探讨曲克芦丁对健康和糖尿病心脏心肌缺血再灌注损伤诱导的 GSK-3β蛋白磷酸化和细胞凋亡的影响。雄性 Wistar 大鼠(n=36,250-300 g)随机分为四组:健康组、糖尿病组、健康曲克芦丁组和糖尿病曲克芦丁组。糖尿病由单次腹腔注射链脲佐菌素(50 mg/kg)诱导,糖尿病期持续 10 周。糖尿病诱导 6 周后,曲克芦丁治疗组每天通过口服灌胃给予 150 mg/kg 曲克芦丁 4 周。将大鼠心脏转移到 Langendorff 仪器中,然后进行 30 min 局部缺血,随后进行 45 min 再灌注。通过 ELISA 测定左心室上清液中心肌肌钙蛋白 I(cTnI)的水平,通过 Western blot 测定总 GSK-3β和磷酸化 GSK-3β的水平,通过 TUNEL 测定组织凋亡。与相应对照组相比,曲克芦丁给药显著降低了健康组和糖尿病组的 cTnI 水平(P<0.05)。此外,曲克芦丁显著增加了糖尿病组和对照组中磷酸化 GSK-3β的水平和磷酸化与总 GSK-3β的比值(P<0.05)。在对照组和糖尿病组中,曲克芦丁给药后组织凋亡水平和凋亡指数也显著降低(P<0.05)。这些发现表明,曲克芦丁通过抑制 GSK-3β活性和随后减少细胞凋亡,在其对再灌注损伤的心脏保护中发挥重要作用。