δ9-四氢大麻酚对糖尿病大鼠心肌缺血再灌注损伤的影响:PTEN/PI3K/Akt 信号通路的作用

IF 1.4 4区 医学 Q4 PHYSIOLOGY
Xiaohua Zhao, Zhao Gao, Wenbin Wen, Shikang Zheng
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引用次数: 0

摘要

尽管目前有最佳治疗方法,但心肌缺血/再灌注(IR)损伤患者的死亡率仍然很高,尤其是合并糖尿病的患者。有必要研究旨在改善糖尿病患者心肌IR损伤预后的潜在治疗方法。我们的目的是确定δ9-四氢大麻酚(THC)对糖尿病大鼠心肌IR损伤的心脏保护作用,并研究磷酸酶和天丝蛋白同源物(PTEN)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路在介导这一作用中的作用。雄性 Wistar 大鼠(8-10 周大,200-250 克;n = 60)通过单次注射链脲佐菌素诱发糖尿病。糖尿病期为 10 周。在糖尿病期的最后 4 周,大鼠腹腔注射 THC(1.5 毫克/千克/天;腹腔注射),单独或与 LY294002 联合使用,然后进行红外干预。再灌注 24 小时后,评估梗塞大小、心脏功能、乳酸脱氢酶(LDH)和心肌特异性肌钙蛋白-I 同工酶(cTn-I)水平、心肌凋亡、氧化应激标记物以及 PTEN、PI3K 和 Akt 蛋白的表达。THC 预处理可明显改善梗死面积和心脏功能,降低 LDH 和 cTn-I 水平(P < 0.05)。它还减少了心肌凋亡和氧化应激,同时下调了 PTEN 的表达,激活了 PI3K/Akt 信号通路(P < 0.05)。LY294002 预处理可取消 THC 的心脏保护作用。本研究揭示了 THC 对红外诱导的糖尿病大鼠心肌损伤的保护作用,并认为其机制可能与通过降低 PTEN 磷酸化增强 PI3K/Akt 信号通路的活性有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impacts of delta 9-tetrahydrocannabinol against myocardial ischemia/reperfusion injury in diabetic rats: Role of PTEN/PI3K/Akt signaling pathway.

Despite the current optimal therapy, patients with myocardial ischemia/reperfusion (IR) injury still experience a high mortality rate, especially when diabetes mellitus is present as a comorbidity. Investigating potential treatments aimed at improving the outcomes of myocardial IR injury in diabetic patients is necessary. Our objective was to ascertain the cardioprotective effect of delta 9-tetrahydrocannabinol (THC) against myocardial IR injury in diabetic rats and examine the role of phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in mediating this effect. Diabetes was induced in male Wistar rats (8-10 weeks old, 200-250 g; n = 60) by a single injection of streptozotocin. The duration of the diabetic period was 10 weeks. During the last 4 weeks of diabetic period, rats were treated with THC (1.5 mg/kg/day; intraperitoneally), either alone or in combination with LY294002, and then underwent IR intervention. After 24 h of reperfusion, infarct size, cardiac function, lactate dehydrogenase (LDH) and cardiac-specific isoform of troponin-I (cTn-I) levels, myocardial apoptosis, oxidative stress markers, and expression of PTEN, PI3K, and Akt proteins were evaluated. THC pretreatment resulted in significant improvements in infarct size and cardiac function and decreases in LDH and cTn-I levels (P < 0.05). It also reduced myocardial apoptosis and oxidative stress, accompanied by the downregulation of PTEN expression and activation of the PI3K/Akt signaling pathway (P < 0.05). LY294002 pretreatment abolished the cardioprotective action of THC. This study revealed the cardioprotective effects of THC against IR-induced myocardial injury in diabetic rats and also suggested that the mechanism may be associated with enhanced activity of the PI3K/Akt signaling pathway through the reduction of PTEN phosphorylation.

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来源期刊
CiteScore
2.30
自引率
5.60%
发文量
36
审稿时长
6-12 weeks
期刊介绍: Chinese Journal of Physiology is a multidisciplinary open access journal. Chinese Journal of Physiology (CJP) publishes high quality original research papers in physiology and pathophysiology by authors all over the world. CJP welcomes submitted research papers in all aspects of physiology science in the molecular, cellular, tissue and systemic levels. Multidisciplinary sciences with a focus to understand the role of physiology in health and disease are also encouraged. Chinese Journal of Physiology accepts fourfold article types: Original Article, Review Article (Mini-Review included), Short Communication, and Editorial. There is no cost for readers to access the full-text contents of publications.
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