| 一.STUDY BACKGROUND AND OBJECTION:Diabetic nephropathy (DN) is one of the severe microvascular complications of diabetes. Now, there are no effective drugs to prevent the progress of DN. Once diabetes patients step into the III or IV stage of DN, the pathological state of it cannot be reversed and it have to step into the V stage of DN (uremia stage) at last. Recent researches indicate that HMG-CoA reductase inhibitor can descend the blood lipid and delay the progress of renal interstitial f ibrosis by inhibiting cell proliferation and interdic intercellular signal transduction but descending blood lipid way.The study use simvastatin to intervent diabetic rats and detect the expression level of a-SMA and CTGF of renal matrix of normal rat group, diabetic rat group and simvastatin treating diabetic rat group by immunohistochemistry way. The index of renal function of three groups had been detected to probe into the effect and mechanism of simvastatin preventing and treating DN.二.METHODS:Male Sprague-Dawley rats(n=60), weighing 200-240g, were grouped randomly into three groups as control group(C), diabetic nephropathy group(D) and diabetic nephropathy group treated with simvastatin(DS). D group and DS group were induced by intraperitoneal injection of streptozotozin (55mg/kg body wt) after 12h fasting, the levels of blood glucose were determined 72h after the injection. The rats with blood glucose levels above 16. 7mmol/l were considered as diabetic rats. DS group were treated by simvastatin (2mg/kg. d, MSD Co. USA) and the other two groups were dealed with water. After 6 weeks and 12 weeks, 10 rats chosen randomly from each group were sacrificed . 24 hours urine were collected to measure albumin excretion. Blood obtained from femoral artery was used measure parameter of biochemistry. Kidneys were exicised, weighed and the left kidneys were dipped to formaldehyde solution immediately and made to be paraffin slices and immunohistochemistry were done. Immunostaining was semiquantitated at 10X magnification by using an image analysis software, the average score of 15 randomly selected was calculated. Results were expressed as mean±Se and statistic analysis is processed in SPSS11.0, P<0.05 is regarded as significant. 三. RESULTS:1. After 6 and 12 weeks , body weight and kidney weight of both D groups and DS groups are lower than C groups, while the ratio of kidney weight /body weight are higher than that of C group (P<0. 05). No significant difference of these parameters exists between D groups and DS groups. In both of diabetes groups kidney weight, body weight in 12 weeks is decreased significantly while kidney weight/body weight ratio is increased compared to 6 weeks(P<0.05).In control group kidney weight and body weight is higher after 12 weeks than after 6 weeks. No significant diversity of kidney weight/body weight presents in C groups between 6 weeks and 12 weeks.2. 24 hours urinary albumin excretion was increased significantly in both of diabetes groups compared with C groups while enhanced more in D groups than DS groups(P<0. 05).3. No significant difference of biochemical parameters such as creatine(Cr), low density lipoprotein (LDL), high density lipoprotein(HDL), triglycerides(TG) exists among all three groups and between 6 weeks and 12 weeks.4. After 6 and 12 weeks, the expression of α-SMA in D groups was increased in the tubulointerstitium compared with C groups(P<0.01). No significant difference of these parameters exists between the 2 diabetes groups. The expression of α-SMA in DS groups was decreased significantly compared with D groups(P<0.01), while higher than C groups after 12 weeks (P<0. 05) .5. The expression of CTGF in D groups was gradually increased in the tubulointerstitium compared with C groups at 6 and 12 weeks(P<0.01). No significant difference of these parameters exists between the 2 diabetes groups. The expression of CTGF in DS groups was markedly decreased compared with D groups(P<0.01), while higher than C groups after 12 weeks(P<0.05).6. Correlative analysis:6. 1 The... |
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