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The Influence Of Finofibrate On The NF-kappa B And MCP-1 Of The Diabetic Rats' Kidney Tissue

Posted on:2006-11-28Degree:MasterType:Thesis
Country:ChinaCandidate:J Y YuanFull Text:PDF
GTID:2144360152481782Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: Diabetic nephropathy (DN) as one of diabetes mellitus'complications, once happens, the progress hardly can be stopped until they go to ESRD. The patients have to be treated with dialyse or be transplanted kidney spending too much. So how to treat DN effitiently is a focus. Fenofibrate as a kide of benzenoxyacetas is used to treat hyperlipemia. Now, it found out that besides its'treatment about hyperlipemia, it has antiinflammatory effect, influence on system of blood coag-ulation and fibrinolysis and opposition to insulin resistance. In the research of fenofibrate preventing on atherosclerosis, it found out fenofibrate could bind with PPAR-αreceptor and make NF-κB activity lower and then the expression of VCAM-1, IL-6 and CRP on endothelial cell lower through antiin-flammatory effects. Researches found out during the developing of DN, there was inflammation in the process. Nuclear factor-kappa B (NF-κB) is the key of inflammation. Clinical and animal experiments had proved that in the monocyt of the circulation and kidney tissue of DN, the activity of NF-κB was higher and it could promote MCP-1 (monocyt chemoattractant protein–1) gene expression. MCP-1 made monocyt chemotaxis which deteriorates DN. Recently a research reported that fenofibrate could make diabetic rats the expression of TGF-β1 lower through treatment on hyperlipemia which suggested that it had kidney protective effects on DN. This research was to create diabetic rats models with STZ and SD rats and treat with fenofibrate. By immunohistochemical assay about NF-κB, MCP-1, we were about to investigate the fenofibrate protective effcts and relationship with NF-κB, MCP-1 on DN in order to supply instruction for clinical treatment. Methods: In the study, healthy male Sprague-Dqawiey rats 36 weighing 180-200g were randomly divided into three groups: the group normal control (group NC), the diabetic rats no treatment (group DN) and the diabetic rats treated with fenofibrate (group DF). Streptozotocin (STZ) 60mg/kg body weight, were celioinjected in group DN and group DF. The levels of blood glucose (BG) were determined 72 hours after injection of STZ and rats with blood glucose 16.7 mmol/L and urine glucose levels 3+-4+ were used as diabetic rats. Group DF was treated with fenofibrate (40mg/kg/d, 5mg/ml) and tap water was given to the other groups. All rats were allowed free access to food and water, excluding from insulin or other glucose-lowering drugs during the experiment.4 weeks and also 8 weeks the following studies were performed in every group. The total mount of urine for 24 hours, body weight, kidney weight, serum, urine and renal tissue dealed with formaldehyde solution (10%) were obtained, then all of the items such as BG(blood glucose), serum lipids consisting of total cholesterol(TC), triglyceride(TG), serum creatine(Scr), urine protein were measured. In addition, the renal hypertrophy index (the ratio of kidney weight to body weight), the total amount of 24 horus urine protein were calculated. Immunohistochemical technique (ABC assay) was used to estimate the expression of NF-κB, MCP-1 and fibronectin (FN) in renal cortex and the renal tissue stained by HE and PAS was observed with light microscope. 1 mm3 renal cortex taken out into glutaral solution (4%) was observed with H-7500 transmission electron microscope. The experimental data was demonstrated in mean±standard deviation. The analysis of variance and q test were used to the significance test by SPSS10.0,a statistic software. Results: The rats in Group DF and Group DN ate and drunk too much with much urine and thinness, but not in Group NC. At 8th week, the level of BG in Group DF was lower than Group DN DF (P<0.05); TG, TC, the amount of 24 hours urine protein and Scr in Group DN increased progressively higher than in Group NC(P<0.01) lower than Group DF(P<0.05). The hypertrophy index in Group DN were higher than Group DF and both in Group NC were lowest(P<0.01). The level of renal NF-κB, MCP-1 and FN were lower in Group DF than in Group DN(P<0.001 and FN P<0.01), but higher than Group NC(P<0.001 and FN P<0.01). Renal GBM in Group DF was thicker than in Group DN, but thinner than in Group NC observed by transmission electron microscope. Conclusion: The experiment proved once more that there...
Keywords/Search Tags:fenofibrate, diabetic nephropathy, monocyt chemoattractant protein-1, nuclear factor-kappaB, fibronectin
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