上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

丙戊酸钠对阿霉素肾病大鼠的肾保护作用

戴 芹1,2，刘 剑1，郝 旭1，杜云蕾1，王伟铭1   

  1. 1.上海交通大学 医学院附属瑞金医院肾脏内科， 上海 200025； 2.上海市浦东新区浦南医院肾脏内科， 上海 200125
  • 出版日期:2014-05-28 发布日期:2014-05-30
  • 通讯作者: 王伟铭, 电子信箱: wweiming@medmail.com.cn。
  • 作者简介:戴 芹（1978—）， 女， 博士生; 电子信箱: dai11qin@sina.com。
  • 基金资助:

    国家重点基础研究发展计划（“973”计划）（2012CB517700）；国家自然科学基金（81270782）；上海市“杏林新星”人才培养项目（ZYSNXD011-RC-XLXX-20130003）；上海市浦东新区优秀青年医师培养计划（PWRq2012-30）

Protective effect of sodium valproate on rats with adriamycin-induced nephropathy

DAI Qin1,2, LIU Jian1, HAO Xu1, DU Yun-lei1, WANG Wei-ming1   

  1. 1.Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China； 2.Department of Nephrology, Punan Hospital, Pudong New Area, Shanghai 200125, China
  • Online:2014-05-28 Published:2014-05-30
  • Supported by:

    National Basic Research Program of China，973 Program，2012CB517700； National Nature Science Foundation of China，81270782； “New Talent in Xingling” Training Project of Shanghai, ZYSNXD011-RC-XLXX-20130003; Outstanding Young Physician Training Program of Pudong New Area of Shanghai, PWRq2012-30

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摘要：

目的 研究组蛋白去乙酰化酶抑制剂丙戊酸钠（VPA）干预对阿霉素肾病大鼠的肾脏保护作用。方法 20只雄性SD大鼠随机分为正常对照组（n=6）和阿霉素肾病组（经阴茎静脉注射阿霉素造模，n=14），后者造模后随机分为模型组和VPA干预组，每组7只。造模8周后，代谢笼留取尿液，腹主动脉采血后处死动物并取肾脏组织，观察各组大鼠血清肌酐(SCr)、尿素氮(BUN)、三酰甘油(TG)、总胆固醇(TC)、谷草转氨酶(GOT）、谷丙转氨酶(GPT)、白蛋白(Alb)和尿微量白蛋白与尿肌酐比值(UACR)的变化。天狼星红染色光学显微镜（光镜）下观察大鼠肾小管间质和肾小球胶原改变；免疫组织化学方法检测肾脏组织α平滑肌肌动蛋白(α-SMA)表达；采用Real-Time PCR技术检测大鼠肾脏组织中Ⅰ型胶原（ColⅠ）、ColⅢ、α-SMA mRNA的表达。结果 与正常对照组比较，阿霉素肾病组大鼠SCr、BUN、TG、TC、UACR均显著升高(P<0.05或P<0.01)，Alb明显降低(P<0.01)，肾小球及肾间质中胶原和α-SMA表达增多；三组大鼠GOT 和GPT的差异无统计学意义（P>0.05）。与模型组比较，VPA干预组SCr、BUN、TC、UACR均显著降低(P<0.05)，肾小球及肾间质中胶原和α-SMA表达减少， Col-Ⅰ、Col-Ⅲ和α-SMA mRNA表达下调。结论 VPA能显著改善阿霉素肾病大鼠的肾功能，减轻肾脏组织纤维化程度，延缓病情的进展。

关键词: 阿霉素肾病, 肾脏纤维化, 丙戊酸钠

Abstract:

Objective To investigate the protective effect of sodium valproate (VPA), an inhibitor of histone deacetylases, on rats with adriamycin-induced nephropathy. Methods Twenty male SD rats were randomly divided into the normal control group (n=6) and adriamycin-induced nephropathy group (the model was established by penial vein injection of adriamycin, n=14). The Adriamycin-induced nephropathy group was further divided into the model group (n=7) and VPA treatment group (n=7). After the model was established for eight weeks, urine samples of rats were collected by metabolism cages and blood samples were extracted from the abdominal aorta. Then rats were sacrificed and renal tissues were obtained. Changes of serum creatinine (SCr), blood urea nitrogen (BUN), triacylglycerol (TG), total cholesterol (TC), glutamic-oxal acetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), albumin(Alb), and urinary albumin to creatinine ratio (UACR) of each group were observed. Changes of the collagen of tubulointerstitium and glomeruli were observed by the optical microscope after being stained by picrosirius. The expression of αsmooth muscle actin (α-SMA) in renal tissues was detected by the immunohistochemistry. The expressions of collagen typeⅠ (ColⅠ), collagen type Ⅲ (ColⅢ), and α-SMA mRNA in renal tissues were determined by the Real-Time PCR. Results Compared to the normal control group, SCr, BUN, TG, TC, and UACR of adriamycin-induced nephropathy group were significantly increased (P<0.05 and P<0.01); Alb was significantly decreased (P<0.01); and the expressions of collagen and α-SMA in tubulointerstitium and glomeruli were increased. The differences of GOT and GPT among three groups were not statistically significant (P>0.05). Compared to the model group, SCr, BUN, TC, and UACR of the VPA treatment group were significantly decreased (P<0.05); the expressions of collagen and α-SMA in tubulointerstitium and glomeruli were decreased; and the expressions of ColⅠ, ColⅢ, and α-SMA mRNA were decreased. Conclusion VPA can significantly ameliorate the renal function of rats with, mitigate the fibrosis of renal tissues, and slow the development of the disease.

Key words: adriamycin-induced nephropathy, renal fibrosis, sodium valproate