天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (12): 1443-1446.doi: 10.11958/20160533

• 实验研究 • 上一篇    下一篇

不同剂量丁苯酞对UUO 小鼠肾组织Nrf-2 表达的影响

曹义甫1 ， 王秀芬2△， 王天智1 ， 解坤3 ， 刘翠红1 ， 李英2   

  1. 1 石家庄市第三医院肾内科 （邮编 050031）； 2 河北医科大学第三医院 （西院） 肾内科； 3 石家庄市心脑血管病医院
  • 收稿日期:2016-06-12 修回日期:2016-09-18 出版日期:2016-12-15 发布日期:2017-01-26
  • 通讯作者: 王秀芬 △通讯作者 E-mail: wangxiufen@medmail.com.cn E-mail:wangxiufen@medmail.com.cn
  • 作者简介: 曹义甫 （1977）， 男， 主治医师， 硕士， 主要从事肾间质纤维化、 肾小球疾病、 血液透析通路研究
  • 基金资助:
    河北省医学科研重点课题计划 （ZD20140125）

The effects of different doses of butylphthalide on Nrf-2 expression in mouse model with unilateral ureteral obstruction

CAO Yifu1 , WANG Xiufen2△, WANG Tianzhi 1 , XIE Kun3 , LIU Cuihong1 , LI Ying2   

  1. 1 Department of Nephrology, the Third Hospital of Shijiazhuang, Shijiazhuang 050031, China； 2 The Third Hospital of Hebei Medical University； 3 Shijiazhuang Cardio-Cerebrovascular Disease Hospital
  • Received:2016-06-12 Revised:2016-09-18 Published:2016-12-15 Online:2017-01-26
  • Contact: WANG Xiufen △Corresponding Author E-mail: wangxiufen@medmail.com.cn E-mail:wangxiufen@medmail.com.cn

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摘要： 摘要： 目的 探讨不同剂量丁苯酞 （NBP） 对单侧输尿管梗阻 （UUO） 小鼠肾间质纤维化的作用， 并探讨核转录因子-E2 相关因子 2 （Nrf-2） 表达水平与肾间质纤维化的关联性。方法 清洁级 CD-1 雄性小鼠 72 只随机均分为低剂量丁苯酞 （NBPL） 组、 高剂量丁苯酞 （NBPH） 组、 假手术 （Sham） 组和模型 （UUO） 组。除 Sham 组外， 均制作 UUO 模型， NBPL、 NBPH 组自术后第 1 天始分别给予 NBP 150 mg/ （kg·d）、 220 mg/ （kg·d） 灌胃。Sham 及 UUO 组亦自术后第 1 天始均给予等量生理盐水灌胃， 每天每公斤体质量入量恒定， 直至处死。各组分别于术后第 3、 7、 14 天处死 6 只小鼠， 取梗阻侧肾组织做免疫组化染色检测Ⅰ型胶原蛋白的表达， Western Blot 检测 7 d 和 14 d 时 Nrf-2、 Ⅰ型胶原蛋白的表达。结果 免疫组化结果显示， UUO 组Ⅰ型胶原蛋白的 IOD 值随时间延长呈增高趋势， Sham 组、 NBPL 组和 NBPH 组呈降低趋势 （P<0.05）。UUO 组、 NBPL 组和 NBPH 组各时点 IOD 值均较 Sham 组增高， NBPL、 NBPH 组较 UUO 组降低， 且 NBPH 组低于 NBPL 组 （P<0.05）。Western Blot 结果显示， 7 d 和 14 d 时， UUO 组、 NBPL 组和 NBPH 组 Nrf-2、 Ⅰ型胶原蛋白 IOD 值均较 Sham 组增高； NBPL、 NBPH 组 Nrf-2 蛋白 IOD 值较 UUO 组升高， 而Ⅰ型胶原蛋白降低； NBPL 组 Nrf-2 的 IOD 值低于 NBPH 组， 而Ⅰ型胶原蛋白高于 NBPH 组 （均 P<0.05）。结论 NBP 对 UUO 小鼠肾间质纤维化有一定的改善作用， 作用机制可能与上调肾组织 Nrf-2的表达， 下调Ⅰ型胶原蛋白的表达有关。

关键词: 输尿管梗阻, 疾病模型, 动物, 胶原Ⅰ型, 丁苯酞, NF-E2相关因子 2, 肾间质纤维化

Abstract: Abstract：Objective To explore the impact of different doses of butylphthalide on renal interstitial fibrosis in mice with obstructive nephropathy, and to discuss the correlation between Nrf- 2 expression level and renal interstitial fibrosis. Methods Totally 72 male CD-1 mice of clean grade were selected and randomly assigned into 4 groups: sham operation group (Sham), model group (UUO), low dose of butylphthalide group (NBPL) and high dose of butylphthalide group (NBPH). In addition to the control group, UUO model was established in other three groups. NBPL group was given NBP 150 mg/(kg· d) by gavage since postoperative day 1， NBPH group was given NBP 220 mg/(kg·d) by gavage. Sham group and UUO group were given equal volume of saline by gavage. Six mice were sacrificed at the third, 7th, 14th day, respectively. The obstructive renal tissue was selected for immunohistochemical staining and Western blot assay. The expression levels of Nrf - 2 and type Ⅰ collagen were detected by Western blot assay. Results The IOD value of type Ⅰ collagen was increased with time in UUO group, and which showed a gradual decreasing trend in Sham group, NBPL group and NBPH group (P < 0.05). The IOD values at different time points were significantly higher in UUO group, NBPL group and NBPH group compared to those of Sham group. The IOD values were significantly decreased in NBPL and NBPH groups than that of UUO group, and IOD value was lower in NBPH group than that of NBPL group (P < 0.05). Western blot assay showed that IOD values of Nrf-2 and type Ⅰ collagen at 7 d and 14 d were increased in UUO group, NBPL group and NBPH group compared with those of Sham group. The IOD values of Nrf-2 protein were increased, and IOD values of type Ⅰ collagen were decreased, in NBPL group and NBPH group than those of UUO group. The IOD value of Nrf - 2 protein was decreased in NBPL group than that of NBPH group, but the IOD value of type Ⅰ collagen was increased in NBPL group than that of NBPH group (P<0.05). Conclusion NBP can improve renal interstitial fibrosis in UUO mice, which may be related with the increased expression of Nrf - 2 and the down-regulated expression of type I collagen.

Key words: ureteral obstruction, disease models, animal, collagen type Ⅰ, dl-3-n·butylphthalide, NF-E2-related factor 2, renal interstitial fibrosis