| Objective:diabetic nephropathy(DN) is a serious chronic implication of diabetes,which has already been one of the main etiological factors of end stage of renal failure.So researching the pathogenesis ,prevention and cure of DN is more important nowadays. Peroxisome proliferator-activated receptors (PPARs) belong to a family of ligand-activated nuclear receptor transcriptional factors and have three members(α,β and γ).PPARs form heterodimers with retinoic X receptor bind to PPAR response elements (PPREs) in the promoter regions of specific target genes to regulate their expressions. PPARγ is expressed at high levels in adipose tissue,colon and activated macrophages,which play important roles in the lipid and glucose metabolisms and the differentiation of adipocyte.Recently more reports demonstrate that PPARγcan inhibit growth and migration of vascular smooth muscle cells and modulate transcription of inflammatory cytokines in macrophages et al,which suggest functions of this receptor distinct from its metabolic activity.Some studies have demonstrated that PPARγ is expressed in the glomeruli of kidney and mesangial cells(MCs) ,which could be activated.As known, MC play a important role in the progression of glomerular lesions.So we hope PPARγwill be the novel therapeutical target for the kidney disease.Thiazolidinediones(TZDs),novel insulin-sensitizing agents, have been recognized as specific synthetic ligands for PPARγ.Those have been shown to attenuate hyperinsulinemia and hyperglycemia in insulin-resistant diabetic animals and human subjects with type 2 diabetes,which are currently widely used as oral antidiabetic agents in clinical therapy.Recently some evidence indicate that TZDs may have direct effects on glomeruli by mechanisms other than their insulin-sensitizing activity.They found TZDs prevented albuminuia and increased glomerular extracellular matrix(ECM)genes expression of STZ induced diabetic rats in the absence of changes in blood glucose.A similar improvement in glomerular lesions was also found in Zucker rats,a model of non-insulin-dependent diabetic glomerulosclerosis,and in 5/6 nephrectomized rats.But the exact mechanisms were not very clear.The current investigation was undertaken by experimental diabetic rats and mesangial cells exposed to high glucose to study the effect of TZDs on the expression and activity of PPARγand genes related to the functional change of mesangial cell and renal pathological abnormality in DN and investigate the possible mechanism of its renal protection,finally provide theoretic basis for the prevention and treatment of DN in the early stage.Methods: (1) Glomerular mesangial cells were separated from SD rats and cultured separately in three different mediums that were normal glucose group (group A),high glucose group (group B) and high glucose with rosiglitazone treated group (group C). Respectively at 12hour ,24hour,48hour after cultured, the cell proliferation was assessed by MTT colorimetric assay. And the expression of PPARγ, c-fos and c-jun were determined by immunocytochemical technique. (2) 36 male SD rats were randomly divided into 3 groups : normal control rats (group A), diabetic rats (group B) and diabetic rats treated with rosiglitazone (group C). Group A contained 10 rats ,the two other groups received single intraperitioneal injection of STZ (60mg/kg) .After 48h, the rats with blood glucose levels greater than 16.7mmol/L were considered as diabetes. The rats were respectively sacrificed at week 4 and 8 after STZ injection.Urine samples of 24 hours were collected before sacrifice. The blood glucose, ratio of kidney to body weight , creatinine clearance rate and 24 urinary protein excretion rate were measured and calculated. The renal tissue were observed with light microscope after periodic acid-Schiff (PAS) staining and with electronic microscope.The level of PPARγ, transforming growth factor-β1 and type Ⅳ collagen in the renal cortex were examined by flow cytometry and immunohistochemical technique. The results of PA...
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