Tim-3在药物性急性肾损伤动物模型中的表达及作用机制

doi:10.6040/j.issn.1671-7554.0.2020.0392

摘要/Abstract

摘要： 目的探索T细胞免疫球蛋白黏蛋白分子3(Tim-3)在急性肾损伤(AKI)中的作用,并研究其作用机制。方法将6~8周C57雄性小鼠随机分为对照组(CTRL组)、顺铂组(AKI组)及顺铂+阻断Tim-3组(RMT组),每组4只,AKI组使用顺铂(20 mg/kg)腹腔注射,构建AKI动物模型,检测肾脏损伤情况与Tim-3表达情况。RMT组使用抗体RMT3-23(200 μg/只)阻断Tim-3分子,建立AKI模型,检测AKI组与RMT组肾脏损伤情况以及Tim-3、自噬相关分子的表达情况。结果肾脏近端小管出现损伤,Western blotting 结果显示 AKI组Tim-3表达水平较CTRL组增加(t=3.876,P=0.008 2)。与AKI组相比,RMT组的NGAL和P62表达水平均增高,但差异无统计学意义(t_NGAL=1.664,P=0.157 0;t_P62=1.991,P=0.103 1),LC3II表达下降,差异有统计学意义(t=5.901,P=0.002 0),自噬受到抑制且肾脏小管损伤加重(P=0.010 1)。结论 Tim-3可以通过调节肾小管上皮细胞自噬活性,减轻顺铂诱导的AKI肾损伤。

关键词: T细胞免疫球蛋白黏蛋白分子3, 急性肾损伤, 顺铂, 自噬, 小鼠

Abstract: Objective To explore the role of T cell immunoglobulin domain and mucin domain protein-3(Tim-3)in acute kidney injury(AKI)and study its mechanism. Methods Six to eight weeks old C57 male mice were randomly divided into the control group(CTRL group), cisplatin group(AKI group), and cisplatin + Tim-3 group(RMT group), 4 in each group. Cisplatin(20 mg/kg)was injected intraperitoneally into the mice in the AKI group to construct the AKI animal model, and kidney injury and Tim-3 expression were detected. In RMT group, the antibody RMT3-23(200 μg/per mouse)was used to block the Tim-3 molecule and to establish an AKI model, and then the kidney injury in the AKI and RMT groups and the expressions of Tim-3 and autophagy-related molecules were detected. Results The renal proximal tubules were damaged. Western blotting results showed that the expression level of Tim-3 in AKI group was higher than that in CTRL group (t=3.876, P=0.008 2). Compared with the AKI group, the expression levels of NGAL and P62 in the RMT group increased without the statistical difference(t_NGAL=1.664, P=0.157 0; t_P62=1.991, P=0.103 1), while the expression of LC3II decreased with a statistical difference(t=5.901, P=0.002 0). The phagocytosis was inhibited and the renal tubular damage was aggravated(P=0.010 1). Conclusion Tim-3 can reduce AKI renal injury induced by cisplatin by regulating the autophagic activity of renal tubular epithelial cells.

Key words: T cell immunoglobulin domain and mucin domain protein-3, Acute kidney injury, Cisplatin, Autophagy, Mouse

中图分类号:

R574

索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1-6.

SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1-6.

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