低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

目的 研究低蛋白饮食对环孢素A（CsA）肾病大鼠肾间质纤维化有无保护作用。 方法 给SD大鼠低盐饮食并注射CsA制作模型。观察对照组、模型组及低蛋白饮食组大鼠的体质量、肾功能、血生化指标及肾脏病理变化,并用实时定量PCR及免疫组化方法检测肾组织转化生长因子β1（TGF-β1）和Ⅰ型胶原（ColⅠ） mRNA及蛋白的表达变化。 结果 模型组和低蛋白饮食组大鼠体质量均显著低于对照组（P < 0.05）;低蛋白饮食组体质量也显著低于模型组（P < 0.05）。模型组和低蛋白饮食组Ccr均显著低于对照组[（0.65±0.15） ml/min、（0.40±0.13） ml/min 比（1.55±0.29） ml/min,P < 0.05],低蛋白饮食组也显著低于模型组（P < 0.05）。模型组及低蛋白饮食组尿渗透浓度均低于对照组（P > 0.05及P < 0.05）。模型组及低蛋白饮食组血清胆固醇均高于对照组（P < 0.05）,而血钙及血清白蛋白无明显变化（P > 0.05）。模型组和低蛋白饮食组肾间质纤维化面积均显著高于对照组（3.60%±0.46%、3.26%±0.75%比0.44%±0.24%,P < 0.05）,而此两组间差异无统计学意义。模型组和低蛋白饮食组TGF-β1及ColⅠ的mRNA及蛋白质表达均较对照组显著上调（P < 0.05）,而两组间差异无统计学意义（P > 0.05）。 结论 低蛋白饮食对CsA肾病大鼠肾损害没有保护作用,反而可能引起大鼠体质量下降。     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with 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 groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

罗格列酮对实验性慢性环孢素肾病的作用

目的 探讨罗格列酮（RSG）对慢性环孢素肾病（CCN）大鼠模型的肾保护作用。 方法 低盐饮食基础上建立CCN大鼠模型，其中1组模型鼠用RSG同时灌胃。分别在实验开始后第14天和第35天处死动物，检测血浆和肾组织血管紧张素Ⅱ（AngⅡ）、AngⅡ1型受体(AT1R)、转化生长因子β1(TGF-β1)、细胞外调节蛋白激酶（p-ERK）、α-SMA和纤连蛋白（FN）的表达。在体外用不同浓度的CsA和RSG孵育NRK细胞。RT-PCR检测肾皮质TGF-β1，Western印迹分析检测FN、AT1R、p-ERK水平。 结果 RSG可改善环孢素A导致的大鼠肌酐清除率的下降[（0.586±0.094）比(1.072±0.105)ml&#8226;min^-1&#8226;kg^-1，P < 0.01]、血浆和肾组织AngⅡ水平增加（P < 0.01）、肾间质单核细胞浸润（P < 0.01）、肾间质纤维化（1.707±0.019 比 2.335±0.022，P < 0.01）、肾组织α-SMA表达增加（P < 0.01）、肾皮质TGF-β1 mRNA水平增加（P < 0.01）、NRK细胞FN、AT1R和p-ERK蛋白水平增加（P < 0.05）。 结论 RSG可能通过减轻炎细胞浸润、影响AngⅡ作用和下调TGF-β1等途径减轻CsA所致的肾组织损伤。     

慢性马兜铃酸肾病肾间质纤维化发病机制的初步探讨

目的制作大鼠慢性马兜铃酸肾病模型,初步探讨该模型肾间质纤维化的发病机制。方法雄性SD大鼠随机分为2组,模型组给关木通浸膏水溶液间断灌胃,对照组仅给自来水灌胃。灌胃后第4、8和12周每组各处死6只大鼠,留取两侧肾脏,应用实时定量反转录聚合酶链反应(realtimequantitativeRT-PCR)和免疫组织化学方法研究两组大鼠肾脏Ⅰ型胶原(ColⅠ)、转化生长因子-β1(TGF-β1)、结缔组织生长因子((CTGF)、纤溶酶原激活物抑制物-1(PAl-1)和金属蛋白酶组织抑制物-1(TIMP-1)的mRNA及蛋白质表达。结果模型组大鼠用药后第4周肾实质ColⅠ、TGF-β1、CTGF、PAI-1及TIMP-1mRNA表达显著上调,分别达对照组的9.31倍、5.16倍、1.79倍、8.66倍及2.54倍(P<0.01或P<0.05);第8周除TIMP-1有所升高外其余指标mRNA表达均有所下降,但与对照组比较差异仍有统计学意义(P<0.01或P<0.05);第12周全部指标mRNA表达继续下降,除CTGF外其余指标与对照组比较差异仍有统计学意义(P<0.01或P<0.05)。模型组大鼠用药后第4周ColⅠ、TGF-β1、CTGF、PAI-1及TIMP-1在肾小管间质的阳性染色面积显著扩大,分别达对照组的2.24倍、1.43倍、1.13倍、1.17倍及1.24倍(P<0.01),第8周和第12周全部指标阳性染色面积持续扩大(P<0.01)。结论慢性马兜铃酸肾病大鼠肾间质     

探讨罗格列酮对减轻环孢素A所致慢性肾毒性的作用及机制

目的 探讨罗格列酮(RGZ)对减轻环孢素A(CsA)所致慢性肾毒性的作用及机制.方法 选择健康、雄性SD大鼠,给予低盐饮食,饲养1周后,随机分成4组.(1)对照组(6只):除低盐饮食外,不给予任何处理;(2)岁格列酮组(6只):低盐饮食,并给予RGZ 5 mg·kg-1·d-1;(3)肾毒性模型组(8只):低盐饮食,并给予CsA 15 mg·kg-1·d-1;(4)治疗十预组(8只):低盐饮食,并给予CsA15 mg·kg-1·d-1和RGZ 5 mg·kg1·d-1.于实验的第2周,每组随机处死3只大鼠,实验的第5周,处死其余的大鼠.检测各组大鼠处死前的内生肌酐清除率(Ccr)和血清白蛋白(ALB)含量;观察各组肾组织的病理学变化;检测各组肾组织中基质金属蛋白酶-9(MMP-9)及金属蛋白酶组织抑制因子-1(TIMP-1)的表达水平.结果 实验第2周,肾毒性模型组和治疗干预组的Ccr及ALB含量均显著下降,第5周下降更为显著,与对照组和罗格列酮组比较,差异有统计学意义(P<0.05);治疗干预组Ccr及ALB下降程度较肾毒性模型组轻,第5周时的Ccr与肾毒性模型组比较,差异有统计学意义(P<0.05).实验第2周,肾毒性模犁组的肾问质可见大量炎症细胞浸润,第5周时,肾小管明显萎缩,肾小球硬化,问质纤维化程度加重;治疗十预组肾组织的损害程度明显较肾毒性模型组轻.肾毒性模型组和治疗十预组在实验的第2周和第5周MMP-9和TIMP-1的表达水平均较对照组和罗格列酮组明显增加(P<0.05),但治疗干预组MMP-9和TIMP-1的表达水平均显著低于同时段肾毒性模型组(P<0.05).结论 罗格列酮可显著降低CsA所致慢性肾毒性大鼠MMP-9和TIMP-1的表达水平,从而减轻CsA对肾脏的慢性毒性作用.     

缬沙坦对糖尿病肾病大鼠肾间质纤维化的作用

目的 探讨缬沙坦在防治糖尿病肾病(DN)大鼠肾间质纤维化( RIF)中的作用及其机制.方法 54只大鼠随机被分为对照组(C组)、DN模型组(D组)和缬沙坦治疗组(T组).D组和T组大鼠分别给予链脲菌素( STZ)一次性腹腔注射建立糖尿病大鼠模型.造模后T组给予缬沙坦混悬液40 mg· kg-1·d-1,分别于实验第4周、第8周和第12周末测血糖、血浆白蛋白、Scr、尿蛋白.Masson染色观察RIF面积.免疫组化法检查肾组织缺氧诱导因子1α( HIF-1α)、金属蛋白酶1组织抑制剂(TIMP-1)、基质金属蛋白酶9(MMP-9)的表达.实时荧光定量PCR测定其mRNA表达.结果 与C组比较,D组及T组大鼠24 h尿蛋白量、Scr均显著升高,肾组织RIF面积、HIF-1α、TIMP-1蛋白及mRNA表达均显著增加,血清白蛋白及肾组织中MMP-9蛋白及其mRNA表达均明显减少,差异均有统计学意义(均P＜0.05).与同时间点D组比较,T组在实验第8周末、第12周末24h尿蛋白、Scr均显著降低,肾组织中RIF面积、HIF-1α、TIMP-1蛋白及其mRNA表达均显著减少,血清白蛋白及肾组织中MMP-9及其mRNA表达均显著增多,差异均有统计学意义(均P＜0.05).结论 缬沙坦可能通过下调HIF-1α、TIMP-1表达,上调MMP-9表达,延缓肾间质纤维化.     

川芎嗪注射液对患糖尿病肾病者肾间质纤维化状态与肾小管功能的影响

目的对川芎嗪注射液对糖尿病肾病患者肾间质纤维化状态与肾小管功能的影响进行分析与探讨。方法选取128例糖尿病肾病患者,以随机方式将其平均分成两组,即对照组与观察组,对对照组患者实施基础治疗,观察组在此基础上加用川芎嗪注射液。比较治疗前后两组患者间尿 NAG、RBP、α1－MG、β2－MG、CIV水平和血清HA、LN 、PCⅢ、ColⅢ、BUN水平,同时测定24h尿蛋白、血浆白蛋白和肾小管对白蛋白的重吸收率。结果治疗2、4周后观察组患者尿α1－MG、NAG、β2－MG、RBP及CIV水平明显低于对照组患者;观察组患者血清HA、LN 、PCⅢ、ColⅢ、BUN水平均显著低于对照组;观察组患者24h尿蛋白显著低于对照组,血浆白蛋白及肾小管对白蛋白的重吸收率则显著高于对照组, P ＜0．05。结论川芎嗪注射液能调节糖尿病肾病患者的尿液及血清相关因子水平,提高肾小管对白蛋白的重吸收率,有效促进肾小管功能及肾间质纤维化状态的改善。     

霉酚酸酯抑制大鼠肾间质纤维化的研究

目的：研究霉酚酸酯（MMF）在单侧输尿管梗阻（UUO）大鼠模型中，能否减少肾小管间质肌成纤维细胞（MyoF)的浸润、增殖及I、Ⅲ型胶原（Col I、ColⅢ）的沉积。方法：将54只大鼠中的36只行左输尿管结扎术，另外18只行假手术。结扎后的大鼠分为模型组和MMF组。术后第5、10及15天分别处死各组中的6只大鼠，用免疫组化方法测定增殖细胞核抗原（PCNA）、α－平滑肌肌动蛋白（α-SMA）及Col I、Col Ⅲ的表达情况。行HE和Masson染色，动态观察肾脏病理学变化。结果：MMF能显著减少肾组织处于增殖状态下的细胞数目和肾小管间质区MyoF的浸润，减轻了Col I、Col Ⅲ的沉积，并有效改善了肾脏的病理学改变。结论：MMF可减少输尿管梗阻后MyoF的浸润并抑制其增殖，从而改善UUO所致的肾脏损伤，提示MMF有潜在的延缓慢性肾功能衰竭进程的作用。     

慢性马兜玲酸肾病大鼠肾小管上皮细胞转分化与肾间质纤维化的关系

关木通等中药引起的慢性马兜铃酸肾病(CAAN)发病主要环节是肾间质内细胞外基质(ECM)蓄积。肌成纤维细胞是肾间质纤维化发生过程中产生ECM的主要细胞。本实验拟通过CAAN大鼠模型肾组织进行研究, 寻找CAAN肾间质纤维化过程中肾小管上皮细胞(TEC)- 肌成纤维细胞转分化(TEMT)的证据并探讨TEMT与肾间质纤维化之间的关系。     

慢性马兜铃酸肾病血小板反应因子1高表达与肾间质纤维化及微血管丢失的关系

目的 探讨血小板反应因子1（TSP-1）与慢性马兜铃酸肾病（CAAN）肾间质纤维化及肾小管周围毛细血管（PTC）丢失的关系。方法 36只SD大鼠被随机分为CAAN模型组（用关木通浸膏水溶液间断灌胃）及对照组（仅自来水灌胃），每组18只。分别于第4、8和12周处死6只大鼠，用肾组织切片做免疫组化染色。对TSP-1、转化生长因子-β1（TGF-β1）、氨基肽酶P（APP）、血管内皮生长因子（VEGF）及Ⅰ型胶原（ColⅠ）的表达进行半定量分析。结果 与对照组比较，模型组大鼠肾间质TSP-1、肾小管TGF-β1及肾间质Col Ⅰ表达均显著上调（P均〈0．01）。3者间表达量呈显著正相关（r=0．925、0．910、0．857，P均〈0．01）。模型组大鼠肾间质APP表达明显下调（P〈0．01），与TSP-1、Col Ⅰ表达量呈显著负相关（r=-0．945、-0．883，P均〈0．01）。模型组肾小管VEGF表达上调（P〈0．01），其表达量与APP呈显著负相关（r=-0．607，P〈0．01），而与TGF-β1星显著正相关（r=0．625，P〈0．01）。结论 TSP-1-TGF-β轴表达增强及与TSP-1相关的PTC丢失均可能参与CAAN肾间质纤维化，而VEGF表达上调为代偿表现。