中国现代医学杂志2018，Vol.28Issue(18)：19-23,5.DOI:10.3969/j.issn.1005-8982.2018.18.004
泰克地那林对四氯化碳诱导小鼠急性肾损伤的治疗作用
Protective effect of histone deacetylase inhibitor Tacedinaline on acute kidney onjury
摘要
Abstract
Objective To investigate the effect of histone deacetylase inhibitor Tacedinaline (CI994) on acute kidney injury in mice. Methods Forty mice were randomly divided into four groups: sham group, CI 994 group, CCl4group, and CCl4+ CI994 group. CCl4was intraperitoneally injected into mice. Mice was administrated with CI994 intraperitoneally 6 hours and 24 hours post CCl4insult. Mice in sham group received normal saline and CCl4 alone was administrated in CCl4group. The levels of urea nitrogen (BUN), creatinine (Src), Cystatin C (Cys C), malondialdehyde (MDA), superoxide dismutase (SOD) and Cytochrome P450 2E1 (CYP2E1) were measured. H&E staining was performed to further confirm tissue injury. Western blot analysis of acetylated histone H3 and chromatin immunoprecipitation of HNF-1a on CYP2E1 promoter were performed. Results CCl4injection induced acute kidney damage as determined by histological analysis and serological testing. Compared with sham group, treatment with CI994 significantly reversed the upregulation of serum BUN, Src and Cys C induced by CCl4(P ＜ 0.05). CCl4induced increase of MDA and CYP2E1 and decrease of SOD were reversed by CI994 treatment (P ＜ 0.05). H&E staining also revealed that CI994 treatment led to recovery of kidney injury induced by CCl4injection. Furthermore, western blot suggested that acetylation of H3 upregulated with CI994 treatment. Immunoprecipitation indicated that binding of HNF-1α on CYP2E1 promoter was significantly increased following CI994 treatment (P ＜ 0.05). Conclusion CI994 protects kidney through downregulation of CYP2E1.关键词
组蛋白去乙酰化酶抑制剂/CI994/急性肾损伤/CYP2E1Key words
histone deacetylase inhibitor/CI994/acute kidney injury/CYP2E1分类
医药卫生引用本文复制引用
程树林,胡春燕,朱平宇,周文浩,龚志勇..泰克地那林对四氯化碳诱导小鼠急性肾损伤的治疗作用[J].中国现代医学杂志,2018,28(18):19-23,5.基金项目
四川省医学会青年创新课题(No:Q16025) （No:Q16025）
