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中药新药芪参滴丸通过 Akt/Nrf2 通路保护心脏免受缺血/再灌注损伤。

Chinese herbal medicine Xinji pill protects the heart from ischemia/reperfusion injury through the Akt/Nrf2 pathway.

机构信息

Department of Pharmacy, Shanxi Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi 710032, P.R. China.

Institute of TCM Research, Shaanxi Provincial Academy of Traditional Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):1551-1558. doi: 10.3892/mmr.2017.6732. Epub 2017 Jun 8.

Abstract

The cardioprotective drugs used for treatment against ischemia/reperfusion (MI/R) injury have been well evaluated and are considered inadequate. The Chinese herbal medicine formula, Xinji pill (XJP) has been used traditionally for the prevention and treatment of ischemic heart diseases for decades. In the present study, the cardioprotective effects of XJP against MI/R injury were assessed in vivo and its possible mechanism was examined. Male Sprague‑Dawley rats were selected for establishing an MI/R model, which was induced by ischemia for 30 min followed by 24 h reperfusion. Drugs and saline were administered intragastrically from day 14 prior to MI/R. Blood samples were collected for biochemical detection. The rats were then sacrificed and cardiac muscle tissues were harvested. The mRNA expression levels of antioxidant genes were measured by reverse transcription‑quantitative polymerase chain reaction and the protein levels were measured by western blotting. Pretreatment with XJP for 14 days protected the heart against I/R‑induced myocardial function disorder, protected against heart injury, as demonstrated by normalized serum levels of lactate dehydrogenase and creatine kinase, and suppressed oxidative stress. XJP markedly upregulated the expression of antioxidant genes, including superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase, and promoted the protein expression of heme oxygenase‑1 and NFE2‑related factor 2 (Nrf2) in the heart tissues. Furthermore, Akt kinase was confirmed to be upstream of Nrf2 in the XJP treatment. LY294002, a specific inhibitor of Akt, significantly eliminated the cardioprotective effects of XJP. In conclusion, these results demonstrated that XJP exhibited notable cardioprotective properties, in which the Akt/Nrf2 signaling pathway may be involved.

摘要

用于治疗缺血/再灌注(MI/R)损伤的心脏保护药物已得到充分评估,但被认为效果不足。中药方剂心迹丸(XJP)已被传统用于预防和治疗缺血性心脏病数十年。在本研究中,评估了 XJP 对 MI/R 损伤的心脏保护作用,并研究了其可能的机制。雄性 Sprague-Dawley 大鼠被用于建立 MI/R 模型,通过缺血 30 分钟后再灌注 24 小时来诱导。在 MI/R 前 14 天开始通过胃内给药给予药物和生理盐水。采集血液样本进行生化检测。然后处死大鼠并采集心肌组织。通过逆转录定量聚合酶链反应测量抗氧化基因的 mRNA 表达水平,并通过蛋白质印迹法测量蛋白质水平。用 XJP 预处理 14 天可保护心脏免受 I/R 诱导的心肌功能障碍,通过正常化血清乳酸脱氢酶和肌酸激酶水平来保护心脏免受损伤,并抑制氧化应激。XJP 显著上调抗氧化基因的表达,包括超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶和谷胱甘肽过氧化物酶,并促进心脏组织中血红素加氧酶-1 和 NFE2 相关因子 2(Nrf2)的蛋白表达。此外,Akt 激酶被确认为 XJP 处理中 Nrf2 的上游。Akt 的特异性抑制剂 LY294002 显著消除了 XJP 的心脏保护作用。总之,这些结果表明 XJP 表现出显著的心脏保护特性,其中 Akt/Nrf2 信号通路可能参与其中。

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