胞外组蛋白对肾小管细胞的损伤作用及其机制

摘要

目的:探讨细胞外组蛋白对肾小管细胞的损伤作用及其相关机制.方法:观察不同浓度(0、50、100、200μg/mL)组蛋白对肾小管细胞(Cos-7细胞)活性的影响;在100μg/mL浓度的组蛋白作用0、12、24、48 h时分别收集Cos-7细胞,用Western blot法检测T细胞免疫球蛋白与黏蛋白域蛋白-1(TIM1)、天冬氨酸特异的半胱氨酸蛋白酶3(caspase3)和受体蛋白Toll样受体2(TLR-2)表达的变化.结果:随着组蛋白药物浓度的增加,Cos-7细胞活性呈下降趋势;100μg/mL组蛋白作用于细胞,随着作用时间的延长,细胞TIM1、caspase3、TLR-2的表达量均显著升高.结论:胞外组蛋白对肾小管细胞存在损伤作用,其机制可能是通过TLR-2信号通路诱导肾小管细胞凋亡.%Objective: To explore the damage effect of extracellular histones on the renal tubular cells (Cos-7 cell) and the relating mechanism.Methods: Cos-7 cells stimulated by different concentration (0, 50, 100, 200 μg/mL) of histones were observed. After treatment with histones (100 μg/mL), Cos-7 cells were collected to detect the expression of T-cell immunoglobulin and mucindomain-containing molecules-1 (TIM1), cysteine aspartate-specific protease 3 (caspase3) and Toll-like receptor-2 (TLR-2) by Western blot at different time points (0, 12, 24, and 48 h).Results: The activity of the Cos-7 cells decreased with the increase of histones concentra-tion. Under the same histones concentration, the expression of TIM1, cleaved-caspase3/t-caspase3 and TLR-2 increased with the stimulation time of the histones.Conclusion: Extracelluar histones induce the kidney injury, and the mechanism may be the induction of renal tubular cell apoptosis through TLR-2 signaling pathway.