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山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (7): 1-6.doi: 10.6040/j.issn.1671-7554.0.2020.0392

• 基础医学 •    

Tim-3在药物性急性肾损伤动物模型中的表达及作用机制

索东阳1,申飞1,郭皓2,刘力畅1,杨惠敏1,杨向东1   

  • 发布日期:2020-07-10
  • 通讯作者: 杨向东. E-mail:yxd683@163.com
  • 基金资助:
    国家自然科学基金(81670660);山东省重点研发计划(GG201809250293)

Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury

SUO Dongyang1, SHEN Fei1, GUO Hao2, LIU Lichang1, YANG Huimin1, YANG Xiangdong1   

  1. 1. Department of Nephropathy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Blood Purification Center, High-tech Zone Branch Hospital, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong, China
  • Published:2020-07-10

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(tNGAL=1.664,P=0.157 0;tP62=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(tNGAL=1.664, P=0.157 0; tP62=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
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