›› 2011, Vol. 31 ›› Issue (2): 158-.doi: 10.3969/j.issn.1674-8115.2011.02.009

• 论著(基础研究) • 上一篇    下一篇

蛋白酶体抑制剂硼替佐米对阿霉素肾病大鼠肾脏的保护作用

周 桥, 卢 颖, 仲 芳, 郝 旭, 李 聪, 郭山脉, 王伟铭, 陈 楠   

  1. 上海交通大学 医学院附属瑞金医院肾脏内科, 上海 200025
  • 出版日期:2011-02-28 发布日期:2011-03-01
  • 通讯作者: 王伟铭, 电子信箱: wweiming@medmail.com.cn。
  • 作者简介:周 桥(1986—), 女, 硕士生;电子信箱: zhouqiao0104@163.com。
  • 基金资助:

    国家自然科学基金(30270613, 30771000);上海市科委重点项目(08dz1900502, 07JC14037);留学回国人员科研启动基金

Renoprotective effect of Bortezomib on adriamycin-induced nephropathy in rats

ZHOU Qiao, LU Ying, ZHONG Fang, HAO Xu, LI Cong, GUO Shan-mai, WANG Wei-ming, CHEN Nan   

  1. Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2011-02-28 Published:2011-03-01
  • Supported by:

    National Natural Science Foundation of China, 30270613, 30771000;Shanghai Science and Technology Committee Foundation, 08dz1900502, 07JC14037;Scientific Research Foundation for the Returned Overseas Chinese Scholars

摘要:

目的 研究蛋白酶体抑制剂硼替佐米(Bortezomib)对经阿霉素诱导的大鼠肾脏组织损伤的干预作用。方法 16只雄性SD大鼠随机分为正常对照组(n=4)和阿霉素肾病组(n=12)。阿霉素肾病组大鼠经阿霉素静脉注射造模后第4周,根据干预方式随机分为模型组、Bortezomib 30 μg/kg干预组和Bortezomib 60 μg/kg干预组,每组4只。观察各组大鼠血、尿生化指标的变化,包括血清肌酐(SCr)、尿素氮(BUN)、白蛋白(Alb)和尿微量白蛋白肌酐比(ACR)等。于建模后第8周心脏采血后处死动物并取肾脏组织,PAS和Masson染色观察肾小管间质和肾小球组织病理学改变;免疫组织化学方法检测肾脏组织α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)和Ⅲ型胶原(Col Ⅲ)表达。结果 与正常对照组比较,模型组和Bortezomib干预组大鼠建模后第2周ACR明显升高。建模后第8周,Bortezomib干预组大鼠血清SCr、BUN和ACR均显著低于模型组,Alb明显高于模型组。肾小管间质损伤指数、肾小球硬化积分、胶原沉积面积百分比及肾脏组织α-SMA、ColⅠ和Col Ⅲ表达,模型组和Bortezomib干预组均显著高于正常对照组,而Bortezomib干预组明显低于模型组,其中Bortezomib 60 μg/kg干预组的效果更为明显。结论 Bortezomib能显著改善阿霉素肾病大鼠的肾脏组织纤维化程度,延缓病情的进展。

关键词: 阿霉素肾病, 硼替佐米, α平滑肌肌动蛋白, Ⅰ型胶原, Ⅲ型胶原

Abstract:

Objective To investigate the effect of Bortezomib on adriamycin-induced nephropathy in rats. Methods Sixteen male SD rats were randomly divided into normal control group (n=4) and adriamycin-induced nephropathy group (n=12). Four weeks after model establishment by intravenous injection of adriamycin, rats in adriamycin-induced nephropathy group were divided into model group, Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group, with 4 rats in each group. The blood and urine parameters including serum creatinine (SCr), blood urea nitrogen(BUN), albumin (Alb) and urinary albumin to creatinine ratio (ACR) in each group were detected. Eight weeks after model establishment, rats were sacrificed after blood sampling from heart, and renal tissues were obtained. The pathological changes of tubulointerstitium and glomerulus were observed with PAS and Masson staining, and the expression of α smooth muscle actin (α-SMA), collagen type Ⅰ (ColⅠ) and collagen type Ⅲ(Col Ⅲ)in renal tissues was detected by immunohistochemistry. Results Compared with normal control group, ACR in model group, Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group were significantly higher 2 weeks after model establishment. Eight weeks after model establishment, serum SCr, BUN and ACR were significantly lower, and Alb was significantly higher in Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group than in model group. For tubulointerstitium injury index, glomerulosclerosis score, percent of collagen deposition area and expression of α-SMA, ColⅠand Col Ⅲ in renal tissues, model group, Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group were significantly higher than normal control group, Bortezomib 30 μg/kg treatment group and Bortezomib 60 μg/kg treatment group were significantly lower than model group, and the treatment effect was most significant in Bortezomib 60 μg/kg treatment group. Conclusion Bortezomib could significantly ameliorate fibrosis of adriamycin-induced nephropathy, and prevent the progression of adriamycin-induced nephropathy in rats.

Key words: adriamycin-induced nephropathy, Bortezomib, α-smooth muscle actin, collagen type Ⅰ, collagen type Ⅲ