Effect of total glucosides of paeony on the expression of nephrin in the kidneys from diabetic rats.
Total glucosides of paeony (TGP), extracted from the traditional Chinese herb root of Paeonia lactiflora pall, have been shown to have a therapeutic role in experimental diabetic nephropathy including albuminuria. Recent investigation has identified nephrin, a podocyte-specific transmembrane protein, as a key regulator in the pathogenesis of diabetic albuminuria. The aim of this study was to investigate whether TGP can attenuate albuminuria through prevention of nephrin loss in the experimental diabetic nephropathy. Fifty male Munich-Wistar rats were obtained from the Experimental Animal Center of Anhui Medical University. These rats were divided into 5 groups (n = 10); normal group, control diabetic group, and 3 TGP treated diabetic groups at different concentrations. Diabetes was induced by streptozotocin, and TGP (50, 100, 200 mg/kg) was orally administered to the 3 TGP treated diabetic groups once a day for 8 weeks, respectively. Blood glucose and 24 hour urinary albumin excretion rate (AER) were measured. The expressions of nephrin, tumor necrosis factor-alpha (TNF-alpha), NF-kappaB p65 and 3-nitrotyrosine (3-NT) protein were determined by immunoinfluorescence or Western blot analysis in the kidneys. Elevated AER was markedly attenuated by TGP treatment in diabetic rats. There was a finely dotted linear epithelial staining of nephrin in normal group glomeruli. In contrast, the staining of glomeruli from untreated diabetic rats was attenuated, more diapersed, and clustered. This diabetic-induced loss of glomerular nephrin expression was prevented in a large degree in TGP-treated diabetic rats. Western blot analysis showed that the expression of nephrin protein was reduced in the kidneys of diabetic rats, but significantly increased in the TGP treatment groups. The expressions of TNF-alpha, NF-kappaB p65 and 3-NT protein were significantly increased in the kidneys of diabetic rats, which were all significantly inhibited by TGP treatment. Our results showed that TGP could decrease AER in diabetic rat, and that its mechanism may be at least partly correlated with upregulation of the expression of nephrin in the kidney.
Zhang
Pei
P
Department of Nephrology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Zhang
Jing-Jing
JJ
Su
Jing
J
Qi
Xiang-Ming
XM
Wu
Yong-Gui
YG
Shen
Ji-Jia
JJ
D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005960:Glucosides / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D029596:Paeonia / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D005960:Glucosides; D008565:Membrane Proteins; C113267:nephrin