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硫辛酸增强缺血后处理介导的糖尿病大鼠缺血/再灌注损伤心肌梗死和细胞凋亡的改善。

Alpha-lipoic acid enhances ischemic postconditioning-mediated improvement of myocardial infarction and apoptosis in diabetic rats with ischemia/reperfusion injury.

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.

出版信息

Can J Physiol Pharmacol. 2023 Dec 1;101(12):682-691. doi: 10.1139/cjpp-2023-0044. Epub 2023 Jul 31.

Abstract

This work evaluated the combined effects of alpha-lipoic acid (ALA) and ischemic postconditioning (Post) on myocardial infarction and cell death in rats with chronic type-II diabetes following ischemia/reperfusion injury. The rats received a high-fat diet and were given one intraperitoneal injection of 35 mg/kg streptozotocin to induce chronic diabetes. They were then pretreated with ALA (100 mg/kg/day, orally) for 5 weeks before undergoing ischemia/reperfusion (I/R) insult. The hearts experienced 35 min regional ischemia through ligating the left anterior descending coronary artery, followed by 60 min reperfusion. The Post protocol involved 6 cycles of a 10/10 s algorithm, applied during the early stage of reperfusion. The use of Post alone did not significantly alter lactate dehydrogenase and infarct size levels, while ALA showed positive effects. Similar findings were observed for apoptotic changes with single treatments. However, the concurrent administration of ALA and Post significantly reduced the protein expressions of Bax, Bax/Bcl2, and cleaved caspase-3 while increasing Bcl2 expression. Additionally, the histopathological findings of the combined therapy were superior to those of single treatments. The concomitant use of ALA and Post effectively inhibited apoptosis, leading to cardiac recovery after I/R injury in diabetic conditions. This strategy could improve outcomes for preserving diabetic hearts following I/R insults.

摘要

这项工作评估了在缺血/再灌注损伤后患有慢性 2 型糖尿病的大鼠中,α-硫辛酸 (ALA) 和缺血后处理 (Post) 联合对心肌梗死和细胞死亡的影响。大鼠接受高脂肪饮食,并接受一次腹腔注射 35mg/kg 链脲佐菌素以诱导慢性糖尿病。然后,它们在经历缺血/再灌注 (I/R) 损伤之前用 ALA(100mg/kg/天,口服)预处理 5 周。心脏通过结扎左前降支冠状动脉经历 35 分钟的区域缺血,随后进行 60 分钟的再灌注。Post 方案涉及在再灌注早期应用 6 个 10/10s 算法循环。单独使用 Post 并没有显著改变乳酸脱氢酶和梗死面积水平,而 ALA 则显示出积极的效果。单一治疗对细胞凋亡变化也有类似的发现。然而,ALA 和 Post 的联合给药显著降低了 Bax、Bax/Bcl2 和 cleaved caspase-3 的蛋白表达,同时增加了 Bcl2 的表达。此外,联合治疗的组织病理学发现优于单一治疗。ALA 和 Post 的联合使用有效抑制了细胞凋亡,导致糖尿病条件下 I/R 损伤后的心脏恢复。这种策略可以改善糖尿病心脏 I/R 损伤后的预后。

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