title: Renal microvascular injury in chronic aristolochic acid nephropathy and protective effects of Cozaar.
abstract: BACKGROUND
  To investigate the renal microvascular injury in chronic aristolochic acid nephropathy (AAN) and the protective effects of Cozaar.
  
  
  METHODS
  Male Sprague-Dawley rats were randomized into three groups. Rats in the model group received Caulis Aristolochiae manshuriensis (CAM) decoction by gavage (10 mL/kg/day); those in the Cozaar group were gavaged with CAM and Cozaar (33.3 mg/kg/day); and those in the control group only received an equal daily volume of saline solution by gavage. Kidney tissues were observed under a light and electron microscope. CD34, caspase-3, and bone morphogenetic protein-7 (BMP-7) were determined by immunohistochemistry, and expressions of angiopoietin (Ang) 1 and 2, Tie-2, BMP-7, and vascular endothelial growth factor (VEGF) mRNA were monitored via real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  (1) The kidney tissue injury in the chronic AAN model group was apparent, compared to the normal structure in the normal control group, and the Cozaar group showed relieved injury. (2) The expression of caspase-3 in the model group was elevated, while expressions of BMP-7 and CD34 were decreased (p < 0.05). Cozaar lessened caspase-3 expression (p < 0.05) and promoted BMP-7 and CD34 expressions (p < 0.05). (3) Real-time PCR demonstrated a downregulation of Ang-1, Tie-2, BMP-7, and VEGF mRNA (p < 0.05) and an upregulation of Ang-2 mRNA (p < 0.01) in the renocortex, while Cozaar upregulated the expression of Ang-1, Tie-2, BMP-7, and VEGF mRNA (p < 0.05).
  
  
  CONCLUSIONS
  Renal microvascular injury was observed in chronic AAN, which was hypothetically correlated with a lack in the expressions of Ang-1, BMP-7, Tie-2, and VEGF and an excess in caspase-3 and Ang-2. Cozaar can significantly ameliorate the renal microvascular injury and protect renal function.
authors: Department of Nephrology, Putuo Hospital, Shanghai University of TCM, Shanghai, PR China.
authors: Yunman
authors: Y
authors: Wang
authors: Wencheng
authors: W
authors: Fu
authors: Hao
authors: H
authors: Wang
authors: Yongping
authors: Y
authors: Liang
authors: Yanan
authors: Y
authors: Wang
authors: Weiguo
authors: W
authors: Yao
authors: Weiwei
authors: W
authors: Chen
authors: Qi
authors: Q
authors: Li
authors: Pei Hao
authors: PH
authors: Ying
authors: Xiaolan
authors: X
authors: Shi
authors: Wen
authors: W
authors: Peng
mesh_terms: D000818:Animals; D034341:Aristolochic Acids / Q000009:adverse effects*; D002908:Chronic Disease; D007668:Kidney / Q000098:blood supply*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D055806:Microvessels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014652:Vascular Diseases / Q000150:complications* / Q000517:prevention & control*
chemical_list: D034341:Aristolochic Acids; C000228:aristolochic acid I; D019808:Losartan