Effects Of Low Protein Diet On The Progression Of Renal Interstitial Fibrosis In Rats With Cyclosporin A-induced Nephropathy

ObjectiveRenal interstitial fibrosis, which strongly correlates with deterioration of renal function, is the critical factor determining prognosis of chronic renal diseases. It is very important for protecting residual renal function to investigate the way how to prevent renal interstitial fibrosis.A lot of studies using animal models of glomerular diseases confirmed that low-protein diet could delay progression of glomerular sclerosis and deterioration of renal function by its effects on diminishing the glomerular hypertension, hyperperfusion and hyperfiltration and reducing the production of fibrogenic cytokines in the glomeruli.This study was designed to investigate whether low-protein diet also has protective effects on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy.MethodsEighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats per group). Control group (C group) received common diet, while model group (M group) received low-salt diet and intervention group (â… group) received lowprotein low-salt diet. After diet adaptation period of one week, C group received daily subcutaneous injection of olive oil (vehicle) 1mg/kg for 5 weeks, while M group andâ… group received daily subcutaneous injection of CsA (diluted into 25mg/mi with olive oil) 1ml/kg for 5 weeks. The following parameters were examined:â‘ Generai properties: body weight, daily food intake and urinary volume of rats;â‘¡Renal function: creatinine clearance (CCr), urinary osmotic pressure and urinaryβ₂-microglobulin;â‘¢Serum biochemical parameters: serum albumin, serum total cholesterol, serum calcium and serum phosphorus levels;â‘£Renal tissue pathologic analysis: semi-quantitative pathlogical analysis on kidney sections of Masson staining under light microscope.⑤Mensurating the expression of transforming growth factor-β1 (TGF-β1) and typeâ… collagen (Colâ… ) in kidney tissue: The mRNA and protein expression was mensurated with reverse transcription-polymerase chain reaction (RT-PCR and realtime PCR) and immunohistochemical staining respectively.Results1. Genaral properties: Compared with the C group, the body weight of rats in M and I groups was significantly reduced (P＜0.05). In addition, the body weight of rats in I group was significantly lower than that in M group (P＜0.05). Compared with the C group, daily food intake of rats in M and I groups was also significantly decreased (P＜0.05), but there was no statistical difference between these two groups (P＞0.05). The urinary volumes of all three groups had no statistical difference (P＞0.05).2. Renal function: Compared with the C group, the CCr in M and I groups was significantly reduced (P＜0.05). In addition, the CCr in I group was significantly lower than that in M group (P＜0.05). Compared with the C group, the urine osmotic pressure in I group was significantly deceased (P＜0.05), and in M group was also deceased, but the difference was not statistically significant (P＞0.05). The urinaryβ2 microglobulin (β2-MG) of all three groups had no statistical difference (P＞0.05).3. Serum biochemical parameters: Compared with the C group, the serum cholesterol levels in M and I groups were significantly increased (P＜0.05), and the serum phosphorus level in I group was significantly decreased (P＜0.05). The levels of serum albumin and serum calcium of all three group had no statistical difference (P＞0.05). 4. Pathologic change: The renal weight/body weight ratios in three groups had no statistical difference (P＞0.05). Compared with the C group, the fibrosis areas of renal interstitium in both M group and I group were significantly increased (P＜0.05). There was no statistical difference between M and I groups (P＞0.05).5. Expressions of TGF-β1 and Col I in renal tissue: the mRNA and the protein expressions of TGF-β1 and Col I in both M group and I group were significantly up-regulated (P＜0.05). There was no statistical difference between M and I groups (P＞0.05).ConclusionThe results of this experiment did not show any renoprotective effect on the progression of renal interstitial fibrosis in rats with cyclosporin A-induced nephropathy from low-protein diet. Instead, due to low-protein diet, the body weight of the rats was significantly decreased.