目的:DNA甲基化在炎症和氧化应激中起重要作用。本研究旨在探讨抑制DNA甲基化对肺缺血再灌注损伤(LIRI)的影响。
方法:我们的研究采用了完全随机的设计。32只大鼠被随机分配到假手术中,LIRI,硫唑嘌呤(AZA),和pluripotin(SC1)组。LIRI中的老鼠,AZA,SC1组接受左肺移植并静脉注射生理盐水,AZA,和SC1。再灌注24小时后,组织学损伤,动脉氧分压与部分吸入氧比,湿/干重比,肺组织中的蛋白质和细胞因子浓度,并对肺组织DNA甲基化进行评价。用AZA或SC1治疗发生低氧血症和复氧的肺内皮。内皮细胞凋亡,趋化因子,活性氧,核因子-κB,并研究了内皮中的凋亡蛋白。
结果:AZA抑制DNA甲基化可减轻肺损伤,炎症,和氧化应激反应,但SC1加重了LIRI损伤.AZA显著改善内皮功能,抑制凋亡和坏死,减少趋化因子,抑制核因子-κB。
结论:抑制DNA甲基化可改善LIRI和细胞凋亡,并通过调节炎症和氧化应激改善肺功能。
OBJECTIVE: DNA methylation plays an important role in inflammation and oxidative stress. This study aimed to investigate the effect of inhibiting DNA methylation on lung ischemia-reperfusion injury (LIRI).
METHODS: We adopted a completely random design for our study. Thirty-two rats were randomized into the sham, LIRI, azathioprine (AZA), and pluripotin (SC1) groups. The rats in the LIRI, AZA, and SC1 groups received left lung transplantation and intravenous injection of saline, AZA, and SC1, respectively. After 24 hours of reperfusion, histological injury, the arterial oxygen partial pressure to fractional inspired oxygen ratio, the wet/dry weight ratio, protein and cytokine concentrations in lung tissue, and DNA methylation in lung tissue were evaluated. The pulmonary endothelium that underwent hypoxemia and reoxygenation was treated with AZA or SC1. Endothelial apoptosis, chemokines, reactive oxygen species, nuclear factor-κB, and apoptotic proteins in the endothelium were studied.
RESULTS: Inhibition of DNA methylation by AZA attenuated lung injury, inflammation, and the oxidative stress response, but SC1 aggravated LIRI injury. AZA significantly improved endothelial function, suppressed apoptosis and necrosis, reduced chemokines, and inhibited nuclear factor-κB.
CONCLUSIONS: Inhibition of DNA methylation ameliorates LIRI and apoptosis and improves pulmonary function via the regulation of inflammation and oxidative stress.