胞外组蛋白对肾小管细胞的损伤作用及其机制

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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、200 μg/mL）组蛋白对肾小管细胞（Cos-7细胞）活性的影响；在100 μg/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；100 μg/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。

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	朱奇凡
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	蔡晖

关键词 ：细胞外组蛋白, 凋亡, TLR-2信号通路, 肾小管

Abstract：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 concentration. 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.

Key words： extracellular histones apoptosis TLR-2 signaling pathway kidney tubules

收稿日期: 2016-12-05

基金资助:国家自然科学基金青年基金资助项目（81200513）；浙江省自然科学基金资助项目（LY17H050006）；浙江省医药卫生科技计划项目（2017KY107）。

通讯作者: 蔡晖，教授，主任医师，Email：hcai3@emory.edu

作者简介: 朱奇凡（1991-），女，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I5/325

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