摘要
目的观察组蛋白去乙酰化酶抑制剂泰克地那林(CI994)对四氯化碳(CCl_4)诱导小鼠急性肾损伤的治疗作用。方法将40只8周龄雄性小鼠随机分为对照组、药物对照组、CCl_4造模组和CI994治疗组,每组10只;对照组腹腔注射生理盐水;CCl_4造模组一次性腹腔注射CCl_4;药物对照组腹腔注射生理盐水,CI994治疗组腹腔注射CCl_4,在注射CCl_4后6和24 h分别给予药物对照组和CI994治疗组腹腔注射CI994。检测各组小鼠血清尿素氮(BUN)、肌酐(Src)和胱抑素C(CysC)水平;对肾组织进行HE染色并检测丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和细胞色素2E1(CYP2E1)mRNA表达水平。结果与CCl_4造模组比较,CI994治疗组小鼠血清BUN、Scr、CysC水平下降(P<0.05);肾组织MDA含量下降,SOD活性上升(P<0.05);HE染色显示CCl_4造模组呈现典型急性肾损伤症状,CI994治疗组肾脏损伤均较CCl_4造模组轻;肾组织CYP2E1m RNA表达水平下降(P<0.05)。结论CI994可减轻CCl_4介导的小鼠急性肾损伤,可能与I相毒物代谢蛋白CYP2E1的表达下调有关。
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,CCl4 group,and CCl4＋CI994 group.CCl4 was intraperitoneally injected into mice.Mice was administrated with CI994 intraperitoneally 6 hours and 24 hours post CCl4 insult.Mice in sham group received normal saline and CCl4alone was administrated in CCl4 group.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 CCl4 injection 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）.CCl4 induced 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 CCl4 injection.Furthermore,western blot suggested that acetylation of H3 upregulated with CI994 treatment.Immunoprecipitation indicated that binding of HNF-1αon CYP2E1 promoter was significantly increased following CI994 treatment（P〈0.05）.Conclusion CI994 protects kidney through downregulation of CYP2E1.
作者
程树林
胡春燕
朱平宇
周文浩
龚志勇
Shu-lin Cheng;Chun-yanHu;Ping-yu Zhu;Wen-hao Zhou;Zhi-yong Gong(Department of Urology,Afliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637000,Chin)
出处
《中国现代医学杂志》
CAS
2018年第18期19-23,共5页
China Journal of Modern Medicine
基金
四川省医学会青年创新课题(No:Q16025)
