阿霉素致小鼠肾功能损伤的机制研究  

Mechanism of Renal Damage Induced by Adriamycin in Mice

作　　者：李丹[1] 丁小明[1] 丁晨光[1] 李杨[1] 朱晓荣 LI Dan;DING Xiaoming;DING Chengguang;LI Yang;ZHU Xiaorong(Department of Kidney Transplantation,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,710061,China)

机构地区：[1]西安交通大学第一附属医院肾移植科,西安市710061

出　　处：《医学分子生物学杂志》2019年第6期506-511,517,共7页Journal of Medical Molecular Biology

基　　金：国家自然科学基金(No.81270548)。

摘　　要：目的 研究Jagged1介导Notch1 及p53-p21 凋亡通路对阿霉素肾病小鼠模型肾功能及病理学影响.方法 通过尾静脉一次性注射阿霉素10 mg/kg构建肾病小鼠模型.比较对照组、模型组、 Jagged1敲除组小鼠肾组织病理学损伤情况, 尿蛋白定量、血清肌酐、尿氮、 ROS、 MDA、 SOD、 GSH水平, Jagged1、Notch1、 p53、 p21、 caspase-3 mRNA及蛋白表达水平.结果 Jagged1基因敲除后, 显著降低了阿霉素引起的肾损伤及肾组织细胞凋亡, 还降低了24 h蛋白尿、血肌酐、尿氮、 ROS、 MDA水平及Jagged1、 Notch1、p53、 p21、 caspase-3 mRNA及蛋白表达水平, 提高了SOD、 GSH水平, 差异均有统计学意义 ( P<0.05).结论 阿霉素可能通过Jagged1介导的Notch1及p53-p21凋亡通路引起模型小鼠的肾功能损伤.Objective To study the effects of Jagged1-mediated Notch1 and p53-p21 apoptosis pathways on renal function and pathology in mice models of adriamycin-induced nephropa-thy.Methods Mice models of nephropathy were constructed by injecting with 10 mg/kg adriamycin through the tail vein.The pathological damage of renal tissues, levels of urine protein quantitation, serum creatinine, urine nitrogen, reactive oxygen radical ( ROS ) , malondialdehyde ( MDA ) , superoxide dismutase ( SOD) and glutathione ( GSH) and mRNA and protein expression levels of Jagged1, Notch1, p53, p21 and caspase-3 were compared among control group, model group and Jagged1 gene knockout group.Results After knockout of Jagged1 gene the, renal damage and re-nal cell apoptosis induced by adriamycin were significantly reduced, and the levels of 24 h proteinu-ria, serum creatinine, urinary nitrogen, ROS and MDA and mRNA and protein expression levels of Jagged1, Notch1, p53, p21 and caspase-3 were decreased while the levels of SOD and GSH were increased ( P <0.05 ) .Conclusion Adriamycin can induce renal damage in mice model through Jagged1-mediated Notch1 and p53-p21 apoptosis pathways.

关 键 词：阿霉素 Jagged1基因 Notch1通路 p53-p21通路 

分 类 号：R692[医药卫生—泌尿科学]