title: DMP-1 attenuates oxidative stress and inhibits TGF-β activation in rats with diabetic kidney disease.
abstract: BACKGROUND
  DMP-1 supplement has a satisfactory effect on diabetic kidney disease in patients with whether T1DM or T2DM. Oxidative stress and TGF-β signal pathway activation are essential in the pathogenesis of DKD. We aim to investigate the effect of DMP-1 on oxidative stress and TGF-β activation in rats with DKD.
  
  
  METHODS
  Male Wistar rats were enrolled and randomly allocated into five groups: Control group, STZ group (60 mg/kg, ip), DMP-1 low dose group (0.5 g/kg/day, ig), DMP-1 medium dose group (1.0 g/kg/day, ig) and DMP-1 high dose group (2.0 g/kg/day, ig). The levels of UREA, BUN, UCr, β2-MG, mALB, NOS, CAT, MDA and T-AOC were measured after 8 weeks treatment. And rats' left kidneys were harvested to detect the expression of TGF-β, Smad2/3 and Smad7 by immunohistochemical analysis.
  
  
  RESULTS
  DMP-1 treatment has protective effects on kidney injury induced by STZ, which is demonstrated as following criteria: (1) a significant reduction in levels of UREA (p < 0.05), BUN (p < 0.05), UCr (p < 0.05), β2-MG (p < 0.05) and mALB (p < 0.05) in rats treated by DMP-1 compared with the ones injected with STZ only; (2) an apparent increment levels of NOS (p < 0.05), CAT (p < 0.05) and T-AOC (p < 0.05), while reduction in level of MDA (p < 0.05) in DMP-1 groups compared with STZ group; (3) a significant inhibition of TGF-β and Smad2/3 overexpression induced by STZ in kidney tissue. What's more, DMP-1 can increase Smad7 expression.
  
  
  CONCLUSIONS
  DMP-1 could slow pathological process and protect kidney from DKD injury by decreasing oxidative stress and inhibiting TGF-β signal pathway activation in rats.
authors.affiliation: a Department of Pharmacology , Jilin University , Changchun , Jilin , China.
authors.forename: Na
authors.initials: N
authors.lastname: Du
authors.affiliation: a Department of Pharmacology , Jilin University , Changchun , Jilin , China.
authors.forename: Shunan
authors.initials: S
authors.lastname: Liu
authors.affiliation: a Department of Pharmacology , Jilin University , Changchun , Jilin , China.
authors.forename: Chongshuang
authors.initials: C
authors.lastname: Cui
authors.affiliation: a Department of Pharmacology , Jilin University , Changchun , Jilin , China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhang
authors.affiliation: b Department of Burn Surgery, The First Hospital of Jilin University , Changchun , Jilin , China.
authors.forename: Jibin
authors.initials: J
authors.lastname: Jia
authors.affiliation: a Department of Pharmacology , Jilin University , Changchun , Jilin , China.
authors.forename: Xia
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D013311:Streptozocin; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D016212:Transforming Growth Factor beta; C526709:yishen huoxue decoction; D013311:Streptozocin
keywords: DMP-1; TGF-β; diabetes mellitus; diabetic kidney disease; oxidative stress