The change of prohibitin in the kidney injury of db/db mice and its intervention

Abstract

Objective To study the molecular mechanisms of prohibitin in the diabetic nephropathy and its effect. Methods C57BLKS/J db/db mice were selected randomly as diabetic model group (DM group, n=8) and the db/m mice were selected as control group (CC, n=8), and C57BLKS/J db/db mice lavage treated with GSPB2 for 10 weeks were considered as treatment group (30mg/kg body weight/day, DMT, n=8). At the end of 18 weeks, fasting blood glucose (FBG), advanced glycation end products (AGEs) and monocyte chemotactic protein 1 (MCP1) were determined. Morphological changes of the kidney tissue were examined by light microscopy and transmission electron microscope. The expression of prohibitin in the kidney tissue was determined by Western blot. Results The body weight was higher in DM groups than in control group at 8, 12, 16, 18 weeks (all P<0.01). The body weight was significantly inhibited at 12, 16, 18 weeks after GSPB2 administration in the DMT group as compared to the DM group (all P<0.05). Serum FBG, AGEs and MCP-1 levels were significantly higher in DM group than in control group (all P<0.01). GSPB2 significantly decreased the serum levels of FBG, AGEs and MCP-1 in db/db mice (all P<0.01). The glomerular volume, mesangial cell proliferation, extracellular matrix in DM group was significantly increased as compared with CC group by light microscopy. GSPB2 significantly reduced the glomerular volume, mesangial cell proliferation in db/db mice. The result of ultrastructural microscopy showed that in DM group, mesangial cell was inserted into the sub-endothelium, basement membrane became thicken, the number of podocytes was decreased and the podocytes were fused, and the thicken basement membrane and podocytes injure were improved in the DMT group. Moreover, the protein expression of prohibitin was higher in DM group than in control group (P<0.01), while GSPB2 could decrease the protein expression of prohibitin (P<0.01). Conclusions The mechanism of protective effects of GSPB2in diabetic nephropathy can be attributed to its anti-glycation, anti-inflammatory and the increase of prohibitin expression, which will provide a theoretical basis for the prevention and treatment of diabetic nephropathy. Key words: Diabetic nephropathy; Ceu prohibitin; Procyanidins