缺血再灌注及顺铂诱导小鼠急性肾损伤模型的建立及评估

doi:10.3969/j.issn.1674-5817.2014.03.004

实验动物与比较医学 ›› 2014, Vol. 34 ›› Issue (3): 187-192.DOI: 10.3969/j.issn.1674-5817.2014.03.004

缺血再灌注及顺铂诱导小鼠急性肾损伤模型的建立及评估

姜燕^1,2, 王葳^1,2, 李泽争^1,2, 程劲², 王巍巍², 张金元²

1.上海中医药大学研究生院, 上海 201203;
2.解放军第四五五医院肾脏科南京军区肾病研究所,上海 200052

收稿日期:2013-09-27 出版日期:2014-06-25 发布日期:2014-06-25
作者简介:姜燕(1986-), 女, 医学硕士,E-mail:404317488@qq.com
基金资助:
上海市优秀青年医学人才培养计划(No. XYQ2011012)

Establishment and Evaluation of Acute Kidney Injury Mice Model by Ischemia Reperfusion and Cisplatin Induction

JIANG Yan^1,2, WANG Wei^1,2, LI Ze-zheng^1,2, CHENG Jin², WANG Wei-wei², ZHANG Jin-yuan²

1. Institute of Postgraduated,Shanghai University of TCM, Shanghai 201203, China;
2. Department of Nephrology, No.455 Hospital of PLA,Reseach Institute of Nephrology of Nanjing Military Area, Shanghai 200052, China

Received:2013-09-27 Online:2014-06-25 Published:2014-06-25

摘要/Abstract

摘要： 目的探讨缺血再灌注及顺铂诱导两种方式建立急性肾损伤小鼠模型的最适条件。方法雄性C57BL/6小鼠随机分为缺血再灌注组、顺铂诱导组; 根据肾缺血再灌注不同时间0 min(sham, 假手术)[30 min、40 min、45 min]及顺铂腹腔注射不同剂量0 mg/kg(control, 对照)[12.5 mg/kg、15 mg/kg、20 mg/kg单次及10 mg/kg两次]分不同亚组,检测血尿素氮(BUN)和肌酐(Scr)水平, HE染色观察肾组织病理变化并根据肾小管坏死程度进行评分(ATN评分); TUNEL法检测肾小管上皮细胞凋亡。结果缺血再灌注组建模24 h后血Scr、BUN和ATN评分明显升高, 与Sham组比较, 差异具有统计学意义(P<0.05), 随着缺血时间的延长, 凋亡阳性细胞数逐渐增多, 肾组织损伤程度加重, 45 min组部分肾小管坏死。顺铂诱导组建模后24 h Scr、BUN和ATN评分逐渐升高,与control组比较,差异有统计学意义(P<0.05),随着顺铂浓度的升高, Scr、BUN上升幅度相对较小, 10 mg/kg两次注射组凋亡阳性细胞数相对较多, ATN评分显示肾小管中度损伤。结论小鼠肾缺血30~40 min是缺血再灌注急性肾损伤模型较为理想的缺血时间; 10 mg/kg两次注射是顺铂诱导的急性肾损伤模型较适宜剂量,缺血再灌注组肾组织损伤程度重于顺铂诱导组。

关键词: 急性肾损伤, 顺铂, 缺血再灌注, 细胞凋亡

Abstract: Objective To evaluate renal tissue damage in acute renal injury model mice established by ischemia reperfusion (I/R) with different renal ischemia times and intraperitoneal injection of cisplatin with different concentrations. Methods The male C57BL/6 mice were randomly divided into the I/R group and cisplatin induction group. All the mice were sacrificed ,whose blood were sampled for detection of serum creatinine(Scr)and urea nitrogen(Bun), the kidneys samples were dyed with HE for observation of the pathological changes and evaluation of acute tubular necrosis score(ATN score). In situ renal tubular epithelial cells apotosis were detected by TUNEL. Results The levels of BUN and Scr and ATN score in I/R group and cisplatin induction group were much higher than those of in the sham group and control group (P<0.05). As to the situation where cisplatin concentration heightened and ischemia times prolonged, the apoptosis cells gradually increased, and the pathological damage in renal tissues was more severe. Conclusion Renal tubular necrosis occurred in some of the ischemia-reperfusion 45 min group. The ideal time of acute ischemia kidney injury is 30~40 min. 10 mg/kg intraperitoneal injection twice is a suitable dose to AKI model induced by cisplatin.The degree of renal tissue injury of the mice was more severely in ischemia-reperfusion group than cisplatin induced group.

Key words: Acute kidney injury, Cisplatin, Ischemia/reperfusion, Cell apoptosis

中图分类号:

Q95-33

姜燕, 王葳, 李泽争, 程劲, 王巍巍, 张金元. 缺血再灌注及顺铂诱导小鼠急性肾损伤模型的建立及评估[J]. 实验动物与比较医学, 2014, 34(3): 187-192.

JIANG Yan, WANG Wei, LI Ze-zheng, CHENG Jin, WANG Wei-wei, ZHANG Jin-yuan. Establishment and Evaluation of Acute Kidney Injury Mice Model by Ischemia Reperfusion and Cisplatin Induction[J]. Laboratory Animal and Comparative Medicine, 2014, 34(3): 187-192.

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缺血再灌注及顺铂诱导小鼠急性肾损伤模型的建立及评估

Establishment and Evaluation of Acute Kidney Injury Mice Model by Ischemia Reperfusion and Cisplatin Induction

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