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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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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