关键词: 8-氧代鸟嘌呤DNA糖基化酶, 顺铂, 急性肾损伤, Th5487, 环鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子

Abstract: Ｏｂｊｅｃｔｉｖｅ：To investigate the role and mechanism of 8-oxoguanine DNA glycosylase (OGG1) in cisplatin-induced acute kidney injury (AKI).
Ｍｅｔｈｏｄｏｌｏｇｙ：Forty-eight C57BL／6 male mice aged 8-10 weeks were used to establish an in vivo animal model. Twenty-four mice were divided into four groups with 6 mice in each group. Cisplatin was injected intraperitoneally for 0h, 24 h, 48 h and 72 h, respectively. The remaining mice were also randomly divided into four groups: saline control group, cisplatin group, saline and Th5487 group, cisplatin and Th5487 group. Saline or cisplatin and Th5487 were injected intraperitoneally. Blood was taken to determine creatinine and urea nitrogen, and renal tissue was taken for pathological analysis. 8-oxoguanine (8-oxoG) content and superoxide dismutase (SOD) activity were detected. The expression of OGG1 and inflammatory protein was verified by Western blot, and the level of mRNA was measured by RT-qPCR. The in vitro cell model of mouse renal tubular epithelial cells induced by cisplatin was established, and the changes of mitochondrial membrane potential(MMP), the production of reactive oxygen species(ROS) and the protein expression were detected.
Ｒｅｓｕｌｔｓ：In AKI induced by cisplatin, the expression of OGG1 was up-regulated, cGAS-STING signal and inflammation were activated, and OGG1 inhibitor Th5487 could alleviate the tissue injury and inhibit the activation of cGAS-STING signal and inflammation induced by cisplatin. In vitro, after cisplatin treatment in renal tubular epithelium, the MMP and ROS concentration increased significantly, and Th5487 could reduce the ROS content and mitochondrial membrane depolarization induced by cisplatin.
Ｃｏｎｃｌｕｓｉｏｎ：In the process of cisplatin-induced AKI, OGG1 can promote renal injury and inflammation through cGAS-STING signal.

Key words: 8-Oxoguanine DNA glycosylase, cisplatin, acute kidney injury, Th5487, cGAS-STING