脂氧素对脂多糖诱导的人近曲肾小管上皮细胞氧化应激的影响及机制

Effect of lipoxin A4 on lipopolysaccharide-induced oxidant stress in human renal tubular epithelial cells and possible mechanisms

目的:研究脂氧素对人近曲肾小管上皮细胞(HK2细胞)氧化应激的影响并进一步探讨其内在机制。方法:分别用脂氧素A4(LXA_4)和(或)脂多糖(LPS)刺激HK2细胞,观察两者对细胞形态的影响;免疫荧光检测LXA_4和(或)LPS对HK2细胞核因子E2相关因子2(Nrf2)核转位的影响,RT-PCR检测LXA_4和(或)LPS对HK2细胞Nrf2及下游二期酶分子表达的影响。结果:与对照组相比,LPS促使细胞崩解、坏死,而LXA_4保护细胞免受损伤;免疫荧光显示,LPS能明显降低Nrf2蛋白的表达,并促进其向胞浆转位,而LXA_4能增加Nrf2蛋白的表达,并促进其向核转位;RT-PCR显示,LPS能明显降低Nrf2及下游二期酶m RNA的表达,而LXA_4能逆转这种效应。结论:LXA_4可以明显抑制LPS诱导的HK2细胞氧化应激,其作用可能是通过上调Nrf2通路实现。

Objective The study aimed to investigate the effect of lipoxin A4 （LXA4） on lipopolysaccharide （LPS）-induced oxidant stress in human renal tubular epithelial cells （HK2 cells） and possible underlying mecha- nisms. MethodsHK2 cells were divided into three groups： Control, LPS and LPS＋LXA4 groups. After ceils were treated with indicated conditions, morphological changes were observed. The expressions of Nrf2 were detected by immunofluorescence and cells were collected for RT-PCR experiments.Results HK2 cells seemed disrupted and necrotic with the administration of LPS. However, LXA4 could prevent ceils from injury induced by LPS. LPS decreased Nrf2 expression and promoted it to translocate to cytoplasm, while LXA4 could increase its expression and promote it to translocate to nucleus. Moreover, LPS could decrease Nrf2 and its downstream molecule mRNA expressions, but LXA4 could reverse this effect. Conclusion Our results demonstrated that LXA4 effectively inhibit- ed HK2 cell oxidant stress via Nrf2 pathway.