| PrefaceProgressive glomerulosclerosis is the common pathologic pathway of various glomemlar diseases and prevention or delay of glomerulosclerosis has become the hot point of research in the field of kidney disease. Uninephrectomy with intravenous injection of adriamycin twice induced chronic renal failure model is a classic one of focal glomerulosclerosis characterized by remnant glomemlar hypertrophy, progressive expansion of extracellular matrix in mesangium and interstitial fibrosis. Rosiglitazone belongs to thiazolidinediones (TZDs), a new kind of antidiabetic agent, and its major function is to enhance the sensitivity of peripheral tissues to insulin by activating peroxisome pro-liferator-activated receptor-r(PPARr). Recently, numerous experimental and clinical evidence have suggested that TZDs can decrease the excretion of urinary protein in diabetic rats and patients with diabetic nephropathy and it can protect glomerular function independently of its capacity to increase insulin sensitivity. Furthermore, in a nondiabetic glomerulosclerosis model, TZDs was effective in preventing the deterioration of renal function. Whether rosiglitazone has this kind of effect on kidney and its mechanism are unknown. In this study, we established uninephrectomized adriamycin - induced glo-merulosclerosis rat model to investigate the protecting effect of rosigli-tazone on the kidney and discuss its possible mechanism.Materials and Methods1. Experimental animalsMale Wistar rats (n=26), weighing 200g-250g, aged 3 months, were randomized to three groups: 1) model rats untreated , n = 10;2) treated rats, n=10;3) normal controls,n=6(sham operated group). After adaptive observation one week , the twenty rats in 1) &2) group were left - nephrectomized , then firstly injected adria-mycin caudal - venously by 5mg/kg one week after the operation and the secondly injection of adriamycin 3mg/kg was carried out the 4th week after the operation. The rats in control group were sham operated, and were injected normal saline with the equal volume at the same time. After the first injection the rats in group 2) were administered orally by rosiglitazone 2mg/kg/d (12 weeks) , giving normal saline of the equal volume to the rats in group1) and group 3). At 0,4, 8,12 weeks, we collect the 24 - hour urine of the rats from each group which were placed individually in metabolic cages. At the 12th weekend , the rats were put to death then kidneys and arterial blood were obtained.2. Indices assayed2. 1 Urinary protein was measured by sulfosalicylic acid turbi-dimetry method.2. 2 Serum creatinine , blood urea nitrogen and serum albumin were detected with automatic biochemical analyzer.2. 3 Kidney morphology: routine HE and PAS staining.2. 4 Calculation of glomerulosclerosis index: RAIJ semiquanti-tation method.2. 5 The TGF-1, Col IV and fibronectin expression were detected by immunohistochemistry (SABC). Immunostaining was semi-quantitated by Floege method.3. Statistical analysisResults were expressed as mean+SD(x+s). Comparisons a-mong 3 groups were analyzed by one - way analysis of variance, followed by LSD multiple comparision test to evaluate statistical difference between 2 groups, p <0.05 is considered as significant.Results1. Urinary protein excretionUrinary protein excretion of group 1) and group 2) were higher than that of group 3 ) , and the urinary protein excretion of group 2) was lower than that of group 1) at 4,8,12 week. There was significant difference among these three groups(p<0.01).2. Blood creatinine , urea nitrogen and albuminBlood creatinine and urea nitrogen levels of group 1) were significantly higher than that of group 3 ) (p<0.01) ; Albumin of group 1) were lower than that of group 3) (p <0. 01). After treatment , blood creatinine and urea nitrogen decreased while albumin increased . There was significant difference between group 2) and group 1) ( p < 0.01).3. Kidney morphologyIn group 1) , we can see mild to moderate glomerular mesangial ce...
|
PDF Full Text Request