摘要
目的:探讨组蛋白甲基化抑制剂DZNep在小鼠肾脏缺血再灌注损伤模型中对肾脏的早期保护作用。方法:18只C57BL/6小鼠随机分成假手术组(sham组)、缺血再灌注损伤组(IR组)和缺血再灌注+治疗组(IR+DZNep组)。后两组建立缺血再灌注损伤模型,IR+DZNep组双侧腹股沟皮下注射DZNep(1mg/kg)100μL。假手术组游离双侧肾蒂但不阻断。术后36h采集标本,评价肾功能和肾组织病理学损伤;通过脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测肾小管上皮细胞凋亡情况;通过检测髓过氧化物酶(MPO)评价炎症细胞的浸润程度;采用实时定量反转录聚合酶链式反应(qRTPCR)检测肾脏组织相关炎症细胞因子水平。结果:肾脏缺血再灌注损伤后36h,与IR组相连,IR+DZNep组小鼠血肌酐和尿素氮水平明显下降(69.17±3.49 vs 103.83±14.62,9.56±1.07 vs 0.75±15.83;P<0.05);病理损伤减轻,肾小管细胞凋亡减少,炎症细胞因子水平降低(P<0.05)。结论:DZNep可以通过抑制细胞凋亡、减轻炎症反应等方式降低小鼠缺血再灌注损伤肾脏的损伤程度,发挥对肾脏的保护作用。
Objective：To study the protective effect of histone methylation inhibitor DZNep on kidney at early stage in the model of renal ischemia reperfusion injury in mice.Methods：18C57BL/6 mice were randomly divided into sham operation group（sham group）,ischemia reperfusion injury group（IR group）and ischemia reperfusion plus therapy group（IR＋DZNep group）.The model of ischemia reperfusion injury was established in the latter two groups.The IR＋DZNep group was given bilateral inguinal subcutaneous injection of DZNep（100μL per mg/kg）.Bilateral renal pedicles were isolated but not clamped.Renal function and histopathological changes were evaluated 36 hafter operation.The apoptosis of renal tubular epithelial cells was detected by TDT-mediated dUTP nick end labeling（TUNEL）assay.Infiltration of inflammatory cells was evaluated through the detection of myeloperoxidase（MPO）.Inflammatory cytokine levels in renal tissue were detected by real-time quantitative reverse transcription polymerase chain reaction（qRT-PCR）.Results：After DZNep treatment,the serum creatinine and urea nitrogen level decreased when compared with IR group（69.17±3.49 vs 103.83±14.62,9.56±1.07 vs 30.75±15.83;P〈0.05）.Apoptotic renal cells in DZNep group also declined than IR group（P〈0.05）.Conclusions：DZNep can reduce the degree of renal ischemia reperfusion injury in mice by inhibiting cell apoptosis and reducing inflammatory reaction,and play a role in protecting the kidney.
出处
《中国临床医学》
2016年第3期261-264,共4页
Chinese Journal of Clinical Medicine
