基础医学与临床 ›› 2017, Vol. 37 ›› Issue (10): 1412-1416.

• 研究论文 • 上一篇    下一篇

单侧输尿管梗阻的大鼠内质网应激相关蛋白表达上调

陶小红1,邱皓1,苗世环2,吕晓云1   

  1. 1. 甘肃省第二人民医院
    2. 兰州大学医学院
  • 收稿日期:2017-04-24 修回日期:2017-06-30 出版日期:2017-10-05 发布日期:2017-09-25
  • 通讯作者: 陶小红 E-mail:693620064@qq.com
  • 基金资助:
    甘肃省卫生行业科研项目

Up-regulation of related protein express under endoplasmic reticulum stress in rats with unilateral ureteral obstruction

  • Received:2017-04-24 Revised:2017-06-30 Online:2017-10-05 Published:2017-09-25

摘要: 目的 探究内质网应激(ERS)相关凋亡通路在单侧输尿管梗阻(UUO)大鼠肾间质纤维化中的作用机制。方法 8周龄Wistar雄性大鼠60只,随机分为假手术组、模型组,每组30只。按昼夜时程,在室温及稳定湿度的条件下用平衡饲料喂养。模型组行左侧输尿管结扎术,假手术组仅分离输尿管不接扎,于术后3天、7天、14天处死各组大鼠。观察两组大鼠HE和Masson染色肾脏病理变化;眼底静脉丛采集血样,分离血清进行血尿素氮、肌酐测定; Western blot检测葡萄糖调节蛋白78(GRP78)、内质网源性转录因子(CHOP)、凋亡相关蛋白半胱氨酸天门冬氨酸蛋白酶3(caspase-3)及caspase-12蛋白表达。结果 与假手术组相比,UUO模型组肾组织病理可见肾小管扩张和肾间质纤维化程度随输尿管梗阻时间延长而渐进性加重;UUO模型组GRP78、CHOP、caspase-3、caspase-12 蛋白表达在术后3d均有上调,随着梗阻时间延长,上述蛋白表达更为显著(p<0.01)。结论 内质网应激相关标志性蛋白在UUO大鼠肾间质纤维化的早期即有在表达变化,长时间的ERS可能导致凋亡发生,caspase-3、12介导的ERS凋亡通路促进了肾间质纤维化不断进展。

关键词: 内质网应激, 肾间质纤维化, 葡萄糖调节蛋白78 , 内质网源性转录因子, 半胱氨酸天门冬氨酸蛋白酶

Abstract: Objective To investigate the mechanism of endoplasmic reticulum stress (ERS) - related apoptosis pathway in renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO). Methods 60 male Wistar rats aged 8 weeks were randomly divided into sham operation group and model group (n = 30). According to the time of day and night, under the condition of room temperature and stable humidity. The rats in the model group were treated with left ureteral ligation. The sham operation group was only treated with no ligation of the ureter, and the rats were sacrificed on the 3 day, the 7 day and the 14 day after operation. Observe the two groups of rats HE and Masson staining of renal pathological changes; fundus venous blood samples were collected and separated serum blood urea nitrogen and creatinine determination; detection of glucose regulated protein 78 (Western blot GRP78), endoplasmic reticulum derived transcription factor (CHOP) and apoptosis related protein cysteine aspartic proteinase 3 (caspase-3 the expression of caspase-12 and protein). Results compared with sham operation group, UUO model group, renal histopathology showed renal tubular dilatation and renal interstitial fibrosis with ureteral obstruction prolonged and progressive aggravation; the expression of UUO GRP78 in the model group, CHOP, Caspase-3, caspase-12 protein in 3D after operation were raised, with the obstruction time prolonged, the expression is more significant (p<0.01). Conclusion endoplasmic reticulum stress related protein marker of early UUO in rat renal interstitial fibrosis with expression change in the long time, ERS may lead to the occurrence of apoptosis, Caspase-3, ERS apoptosis pathway 12 mediated promote renal fibrosis development.

Key words: endoplasmic reticulum stress, renal interstitial fibrosis, glucose regulated protein 78, endoplasmic reticulum derived transcription factor, cysteine aspartic proteinase