Abstract:
Oxidative stress-induced apoptosis is an important pathological process in renal ischemia/reperfusion injury (RIRI). Theaflavin (TF) is the main active pigment and polyphenol in black tea. It has been widely reported because of its biological activity that can reduce oxidative stress and protect against many diseases. Here, we explored the role of theaflavin in the pathological process of RIRI. In the present study, the RIRI model of 45 min ischemia and 24 h reperfusion was established in C57BL/6 J male mice, and theaflavin was used as an intervention. Compared with the RIRI group, the renal filtration function, renal tissue damage and antioxidant capacity of the theaflavin intervention group were significantly improved, while the level of apoptosis was reduced. TCMK-1 cells were incubated under hypoxia for 48 h and then reoxygenated for 6 h to simulate RIRI in vitro. The application of theaflavin significantly promoted the translocation of p53 from cytoplasm to nucleus, upregulated the expression of glutathione peroxidase 1 (GPx-1) in cells, and inhibited oxidative stress damage and apoptosis. Transfection with p53 siRNA can partially inhibit the effect of theaflavin. Thus, theaflavin exerted a protective effect against RIRI by inhibiting apoptosis and oxidative stress via regulating the p53/GPx-1 pathway. We conclude that theaflavin has the potential to become a candidate drug for the prevention and treatment of RIRI.
摘要:
氧化应激诱导的细胞凋亡是肾缺血再灌注损伤(RIRI)的重要病理过程。茶黄素(TF)是红茶中主要的活性色素和多酚。由于其生物活性,可以减少氧化应激并预防许多疾病,因此已被广泛报道。这里,探讨茶黄素在RIRI病理过程中的作用。在本研究中,建立C57BL/6J雄性小鼠缺血45min、再灌注24h的RIRI模型,茶黄素被用作干预措施。与RIRI组相比,肾脏过滤功能,茶黄素干预组肾组织损伤和抗氧化能力明显改善,而细胞凋亡水平降低。将TCMK-1细胞在缺氧下孵育48小时,然后复氧6小时以体外模拟RIRI。茶黄素的应用显著促进p53从细胞质到细胞核的易位,上调谷胱甘肽过氧化物酶1(GPx-1)在细胞中的表达,并抑制氧化应激损伤和细胞凋亡。p53siRNA转染可以部分抑制茶黄素的作用。因此,茶黄素通过调节p53/GPx-1通路抑制细胞凋亡和氧化应激对RIRI具有保护作用。我们得出结论,茶黄素有可能成为预防和治疗RIRI的候选药物。