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The Study Of Protection Of Pioglitazone On Kidney Of Diabetic Rats And Its Effects On Cell Apoptosis

Posted on:2005-04-04Degree:MasterType:Thesis
Country:ChinaCandidate:Q ChenFull Text:PDF
GTID:2144360125950590Subject:Internal Medicine
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Diabetes is a group of metabolic diseases, whose incidence is increasing year by year with the economical development. Primary long-term impairments of diabetes to human body are dysfunction and failure of various organs. Diabetes nephropathy(DN) is one of major chronic complications, which induce to disability and decreasing survival quality. Although the pathogenesis of diabetes nephropathy have been studied, it has not been disclosed completely and now also focusing on metabolism disorder theory. There were many studies from internal and foreign investigations had suggested that tall glucose level acting as a subnecrotic injury agent,it can induce apoptosis increasing, and influence to tubular reabsorption and excretion functions, Apoptosis is associated with albuminuria in the early DN phase. Relationship between proteinuria acting as independent risk factor and renal function damage degree is positive correlation. Decreasing proteinuria play an important action of prevention and halt to DN occurrence and progression, There has made a big progress about the molecular pathogenesis of diabetes nephropathy. Cell apoptosis is associated with the occurrence and development of DM and its complications, Through the profound studies of the relations of gene regulation,signal convection about cell apoptosis and disease,Cell apoptosis is regulated by various factors.Bcl-2 is a gene family associated with apoptosis, it makes an important role on cell apoptosis. Recently studies found that nuclear transcription factor is the cross point of various signal conduction pathway, which has been related with the metabolism of lipid, sugar and greatly involved in molecular pathogenesis of diabetes nephropathy. Perxisome proliferator-activated receptors–gamma (PPAR gamma) is one of the nuclear hormone recepter superfamily of ligand -activated transcription factors. Thiazolidinediones (TZDs) are ligands for PPAR.They can bind with PPAR and activatate transcription factor and regulate adipogenesis and insulin-mediated glucose metabolism. TZDs not only have demonstrated significant utility as insulin – sensitizing agents but also have demonstrated their effects on decreasing albuninnuria in the streptozotocin (STZ) -induced diabetic rat without lowering blood glucose.This indicated that TZDs have many other actions, especially in decreasing albuminuria in early diabetic nephropathy stage except increasing insulin sensibitity. This study observes that effects of pioglitazone on apoptosis and its relation bcl-2 and bax protein in the streptozotocin (STZ) -induced diabetic rats.The aim is to find out mechanisms of TZDs on treatment of diabetes nephropathy . Wistar rats(n=50) were randomly divided into following groups: normal control group(NC);normal control group treated with pioglitazone (NCT);diabetese mellitus group(DM);DM group treated with pioglitazone (DMT).NCT and DMT were treated with pioglitazone (3mg/kg.d) by gavage.The animals of DM and DMT(n=29) were induced by STZ.Blood glucose level was always keeped at above 16.67mmol/L in experiment duration.After 12 weeks of treatment with pioglitazone, There were 40 rats accorded with standard study. The animals were killed and renal morpho -logical examination were performed. Blood pressure,blood glucose ,24hour urinary protein and kidney weight to body weight ratio were detected. Glomerular exracellular matrix(ECM) accumulation and glomerular mesangial cell proliferation and base-membrane thickness were observed by lightmicroscope and electromicroscope. 24-hour urinary protein and kidney weight to body weight ratio of DM group were significantly increased compared with NC and NCT(p<0.05). 24-hour urinary protein and kidney weight to body weight ratio of DMT were decreased compared with that of DM(P<0.05).There were no significant difference between NC and NCT (P>0.05). Glomerular exracellular matrix(ECM) accumulation and glomerular mesangial cell proliferation and base-membrane thickness were significantly higher in DM group than the other groups.(P<0...
Keywords/Search Tags:Thiazolidinediones(pioglitazone), diabetic nephropathy, proteinuria, diabetic rat cell apoptosis, correlation protein of apoptosis bcl-2/bax
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