PDF(Pubmed)
Abstract：
Tranilast, a synthetic derivative of a tryptophan metabolite, can be used to treat heart diseases. However, the specific mechanism underlying the effect of tranilast on ischemia-reperfusion (I/R) injury-induced cardiomyocyte apoptosis remains unclear. Therefore, the present study aimed to determine if tranilast could attenuate I/R-induced cardiomyocyte injury. A hypoxia/reoxygenation (H/R) model of H9c2 cardiomyocytes was established to simulate I/R-induced cardiomyocyte injury. The viability, apoptosis, inflammation and oxidative stress in H/R-induced H9c2 cells following treatment with tranilast were evaluated by Cell Counting Kit-8 and TUNEL assay. Commercially available kits were used to detect the levels of inflammatory markers and oxidative stress indicators. In addition, the expression levels of the apoptosis- and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NF-κB signalling pathway-associated proteins were detected by western blotting. The levels of reactive oxygen species were determined using 2\',7\'-dichlorofluorescin diacetate assay kit. The viability of H9c2 cells was decreased following induction with H/R. However, treatment with tranilast increased viability while decreasing apoptosis, oxidative stress and inflammatory response in H/R-induced H9c2 cells by activating Nrf2/HO-1/NF-κB signalling. Furthermore, treatment with ML-385, an Nrf2 inhibitor, reversed the effects of tranilast on H/R-induced H9c2 cells. In conclusion, the results of the present study suggested that tranilast could attenuate I/R-induced cardiomyocyte injury via the Nrf2/HO-1/NF-κB signalling pathway.
摘要：
Tranilast,色氨酸代谢物的合成衍生物，可用于治疗心脏病。然而,曲尼司特对缺血再灌注(I/R)损伤诱导的心肌细胞凋亡的作用机制尚不清楚.因此,本研究旨在确定曲尼司特是否可以减轻I/R诱导的心肌细胞损伤。建立H9c2心肌细胞缺氧/复氧(H/R)模型,模拟I/R诱导的心肌细胞损伤。生存能力,凋亡，通过细胞计数试剂盒-8和TUNEL测定评价用曲尼司特处理后H/R诱导的H9c2细胞中的炎症和氧化应激。市售试剂盒用于检测炎症标志物和氧化应激指标的水平。此外,免疫印迹法检测细胞凋亡及核因子红细胞相关因子2(Nrf2)/血红素加氧酶-1(HO-1)/NF-κB信号通路相关蛋白的表达水平。使用2'确定活性氧的水平，7'-二氯荧光素二乙酸盐测定试剂盒。H/R诱导后，H9c2细胞的活力降低。然而,曲尼司特治疗增加了活力，同时减少了细胞凋亡，通过激活Nrf2/HO-1/NF-κB信号在H/R诱导的H9c2细胞中的氧化应激和炎症反应。此外，用Nrf2抑制剂ML-385治疗，逆转曲尼司特对H/R诱导的H9c2细胞的作用。总之,本研究结果表明曲尼司特可通过Nrf2/HO-1/NF-κB信号通路减轻I/R诱导的心肌细胞损伤。
