Yu Qian, Li Xin, Cao Xia
School of Pharmaceutical Sciences, Jilin University, China; Pharmaceutical Department of China-Japan Union Hospital of Jilin University, China.
Pharmaceutical Department of China-Japan Union Hospital of Jilin University, China.
Biomed Pharmacother. 2017 Jun;90:1-7. doi: 10.1016/j.biopha.2017.03.025. Epub 2017 Mar 21.
As we all know, oxidative stress was one of the most important causes of ischemia-reperfusion injury. And it was reported that Nrf-2 as an important regulator for oxidative stress could be activated by Linarin. Thus it would be interesting to find whether Linarin could inhibit ischemia-reperfusion injury through activating Nrf-2.
In this study, cell activity was detected by MTT assay and caspase-3 activity detection kit. And the expressions or activities of some signal proteins were evaluated by western-blot or activity detection kits. At last, the effect and mechanism of Linarin on heart tissues were verified in the ischemia-reperfusion model of isolated hearts.
The proliferation activity of cell was inhibited while the apoptosis rate was increased after hypoxia-reoxygenation. However, Linarin could inhibit these two variations. It was found that these effects of Linarin were related with the activation of Nrf-2 through PI3K/Akt signaling pathway. Meanwhile, the anti-oxidative enzymes, regulated by Nrf-2, were enhanced to against the oxidative stress caused by hypoxia-reoxygenation. And with the inhibition of oxidative stress, some proliferation and apoptosis related proteins such as NF-kB and Cytochrome C were adjusted to support the viability of cells. At last, these results were verified in the ischemia reperfusion experiment of isolated hearts.
From this study, we assured that LIN could protect myocardial tissue from ischemia-reperfusion through activating Nrf-2.
众所周知，氧化应激是缺血再灌注损伤最重要的原因之一。据报道，作为氧化应激重要调节因子的Nrf-2可被蒙花苷激活。因此，探究蒙花苷是否能通过激活Nrf-2来抑制缺血再灌注损伤将是很有意义的。
在本研究中，通过MTT法和caspase-3活性检测试剂盒检测细胞活性。并通过蛋白质免疫印迹法或活性检测试剂盒评估一些信号蛋白的表达或活性。最后，在离体心脏缺血再灌注模型中验证蒙花苷对心脏组织的作用及机制。
缺氧复氧后细胞增殖活性受到抑制，凋亡率升高。然而，蒙花苷可以抑制这两种变化。发现蒙花苷的这些作用与通过PI3K/Akt信号通路激活Nrf-2有关。同时，由Nrf-2调节的抗氧化酶增强，以对抗缺氧复氧引起的氧化应激。随着氧化应激的抑制，一些与增殖和凋亡相关的蛋白如NF-κB和细胞色素C被调节，以维持细胞的活力。最后，这些结果在离体心脏缺血再灌注实验中得到验证。
通过本研究，我们确定蒙花苷可通过激活Nrf-2保护心肌组织免受缺血再灌注损伤。
