| Objective To analyze the protective effect of retinoic acid (RA) on kidneysof rats with diabetic nephropathy (DN) and explore the molecular mechanism. Methods DN rat models were established by left nephrectomy combined with continuous high-fat diet and intraperitoneal injection of STZ. The rats with DN after successful modeling were randomly divided intomodel group,glibenclamide group,high-dose RA group,medium-dose RA group and low-dose RAgroup. The glibenclamide group was treated with glibenclamide at 5 mg/kg. The high-dose RA group, the medium-dose RA group and the low-dose RA groupwere treated with 15 mg/kg, 10 mg/kg and 5 mg/kg of RA, respectively. The model group and the normal control group were treated with same volume of normal saline. The administration method was continuous gavage for six weeks. Body mass, kidney indexes, content of 24h urine protein, urinary excretion, blood urea nitrogen (BUN), serum creatinine (Scr) and fasting blood glucose (FBG) were compared among groups. The expression levels of TGF-β1 pathway and related downstream regulatory proteins in renal tissues were determined by Western blotting. Results Body mass of the model group was significantly lower while the renal coefficient, content of 24h urine protein, urinary excretion, BUN, Scr and FBG were significantly higher than those in the normal control group (P<0.05). Body mass of the high-dose RA group, the medium-dose RA group, the low-dose RA group and the glibenclamide group was significantly higher while kidney index, content of 24h urine protein, urinary excretion, BUN, Scr and FBG were significantly lower than those in the model group (P<0.05). HE staining showed that there was no hyperplasia of glomerular mesangium, tubular atrophy or infiltration of inflammatory cells in renal interstitiumin the normal control group.However, there were increased glomerular mesangial matrix, some atrophic kidney tubules with dilatation of the lumen, glycogen vacuoles in proximal tubular epithelial cellsand focal chronic inflammatory cell infiltration in renal interstitium in the model group. There was no obvious hyperplasia of glomerular matrix and reduced area of atrophic kidney tubules in the glibenclamide group, the high-dose RA group, the medium-dose RA group and the low-dose RA group. There was no significant difference in the expression of p38MAPK or Smad2/3 among the groups (P>0.05). Nephrin and podocin were significantly lower while p-p38MAPK, TGF-β1, Caspase-3and Smad2/3 were significantly higher in the model group than in the normal group. Besides, Nephrin and podocin were significantly lower while p-p38MAPK, TGF-β1, Caspase-3 and Smad2/3 were significantly higher in the high-dose RA group, the medium-dose RA group and the low-dose RA group thaninthe model group (P<0.05). Conclusions RA can relieve kidney swelling in rats with DN, reduce urine output and urine protein, lower blood sugar and improve renal function by inhibiting the TGF-β1 pathway, playing a renal protection role. |
