α -硫辛酸促进缺血后适应介导的糖尿病缺血再灌注损伤大鼠心肌梗死和细胞凋亡的改善。

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY Canadian journal of physiology and pharmacology Pub Date : 2023-12-01 Epub Date: 2023-07-31 DOI:10.1139/cjpp-2023-0044
Sanaz Gholami, Reza Badalzadeh, Alireza Alihemmati
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引用次数: 0

摘要

本研究评估了α -硫辛酸(ALA)和缺血后适应(Post)对慢性ii型糖尿病大鼠缺血再灌注损伤后心肌梗死和细胞死亡的联合作用。大鼠给予高脂饮食,腹腔注射链脲佐菌素35 mg/kg诱导慢性糖尿病。然后给予ALA (100 mg/kg/天,口服)预处理5周,然后进行缺血/再灌注(I/R)损伤。结扎左冠状动脉前降支,局部缺血35 min,再灌注60 min。Post方案包括6个周期,10/10秒算法,应用于再灌注早期。单独使用Post没有显著改变乳酸脱氢酶和梗死面积水平,而ALA显示出积极的作用。单次处理的细胞凋亡变化也有类似的结果。然而,ALA和Post同时给药可显著降低Bax、Bax/Bcl2的蛋白表达,并使caspase-3断裂,同时增加Bcl2的表达。此外,联合治疗的组织病理学结果优于单一治疗。同时使用ALA和Post可有效抑制细胞凋亡,促进糖尿病I/R损伤后心脏恢复。这种策略可以改善I/R损伤后保存糖尿病心脏的结果。
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Alpha-lipoic acid enhances ischemic postconditioning-mediated improvement of myocardial infarction and apoptosis in diabetic rats with ischemia/reperfusion injury.

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.

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来源期刊
CiteScore
4.00
自引率
4.80%
发文量
90
审稿时长
3-8 weeks
期刊介绍: Published since 1929, the Canadian Journal of Physiology and Pharmacology is a monthly journal that reports current research in all aspects of physiology, nutrition, pharmacology, and toxicology, contributed by recognized experts and scientists. It publishes symposium reviews and award lectures and occasionally dedicates entire issues or portions of issues to subjects of special interest to its international readership. The journal periodically publishes a “Made In Canada” special section that features invited review articles from internationally recognized scientists who have received some of their training in Canada.
期刊最新文献
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