Atorvastatin alleviates iodinated contrast media-induced cytotoxicity in human proximal renal tubular epithelial cells
Atorvastatin alleviates iodinated contrast media-induced cytotoxicity in human proximal renal tubular epithelial cells
复制标题
阿托伐他汀减轻碘造影剂诱导的人近端肾小管上皮细胞的细胞毒性
DOI：
10.3892/etm.2017.4859
复制
发表时间：
2017
影响因子：
2.7
通讯作者：
Tang Mi-Mi
中科院分区：
文献类型：
--
作者：
Liu Gai-Ling;Lei Rong;Duan Shao-Bin;Luo Min;Xu Qian;Liu Gai-Ling;Tang Mi-Mi
造影剂（CM）诱发肾病（CIN）是血管内应用放射性造影剂的严重并发症。目前，还没有药物被批准用于预防CIN。本研究旨在探讨阿托伐他汀对碘化CM诱导的人近端肾小管上皮细胞毒性的影响及其可能机制。评估了碘海醇（50、100和200 mg I/ml）的细胞毒性作用和阿托伐他汀预处理（1、20和40 μ M）的保护作用。通过MTT细胞活力和乳酸脱氢酶测定评价碘海醇的细胞毒性。流式细胞仪检测凋亡细胞数。透射电镜观察HK-2细胞形态学变化。采用逆转录-定量聚合酶链反应（RT-PCR）方法检测NOX 4和p22 phox mRNA的表达。用碘海醇诱导HK-2细胞毒性。阿托伐他汀被鉴定为显著减轻由碘海醇诱导的细胞活力抑制。值得注意的是，40 μ M阿托伐他汀还显著降低了细胞内NOX 4和p22 phox的mRNA表达，以及凋亡细胞的百分比。此外，阿托伐他汀预处理可减轻损伤细胞的形态学变化特征。这些结果表明，阿托伐他汀对HK-2细胞对碘海醇诱导的细胞毒性的保护作用，通过下调NOX 4和p22 phox。因此，阿托伐他汀是一种潜在的预防CIN的治疗药物，需要进一步研究。
Contrast media (CM)-induced nephropathy (CIN) is a serious complication of intravascularly applied radiocontrast media. At present, no drugs have been approved for the prevention of CIN. The present study aimed to explore the effects and potential mechanisms of atorvastatin on iodinated CM-induced cytotoxicity in the human proximal renal tubular epithelial cells. The cytotoxic effect of iohexol (50, 100 and 200 mg I/ml) and the protective effect of atorvastatin pretreatment (1, 20 and 40 mu M) were assessed. The cytotoxicity of iohexol was evaluated via the MTT cell viability and lactate dehydrogenase assays. The amount of apoptotic cells was determined by flow cytometry. Morphological changes in HK-2 cells were observed via transmission electron microscopy. The mRNA expression of NOX4 and p22phox was measured through reverse transcription-quantitative polymerase chain reaction analysis. The cytotoxicity was induced by iohexol in HK-2 cells. Atorvastatin was identified to significantly alleviate the suppression of cell viability induced by iohexol. Notably, 40 mu M atorvastatin also significantly reduced the mRNA expression of intracellular NOX4 and p22phox, and the percentage of apoptotic cells. Furthermore, morphological changes characteristic of injured cells were alleviated by atorvastatin pretreatment. These results suggest that atorvastatin exhibits a protective effect on HK-2 cells against iohexol-induced cytotoxicity through the downregulation of NOX4 and p22phox. Thus, atorvastatin is a potential therapeutic agent for the prevention of CIN and required further study.