The Mechanisms By Which Lipid Leads To Renal Injury In Diabetic Nephropathy

Part 1. The effects of diet-induced hyperlipidemia on renal injury of STZ-induced SD diabetic rats and on expression of TGF-β, TβRII, p-Smad2 and Col IV in the kidneyObjective To investigate the relationship between diet-induced hyperlipidemia and renal injury in STZ-induced diabetic rats, and explore the mechanism by which hyperlipidemia leads to renal injury through examining expression of transforming growth factor betal (TGF-β1), TGF-β type II receptor (TβR II), phosphorylated Smad2 (p-Smad2) and collagen IV (Col IV) in the kidney.Methods Diabetic rats and non-diabetic rats were fed with either normal fat diet or high fat diet for 16 weeks. The blood levels of triglyceride, cholesterol and glucose were monitored at 4 weeks intervals throughout the experiment. Prior to sacrifice, animals were placed in metabolic cages for collection of urine over a 24-h period for two consecutive days, and urinary albumin in the supernatants was determined by enzyme-linked immumosorbent assay (ELISA). At the end of experiment, blood urea nitrogen (BUN), creatinine, triglyceride and cholesterol were measured on a auto-analysis system. The disposed of ECM in glomeruli was detected by periodic-acid Schiff staining (PAS staining). Expression of TGF-β1, TβRII and Col IV mRNA in renal cortex were examined by Reverse Transcriptase-PCR Analyses, and TβRII and p-Smad staining in glomerular cells was detected by Immunohistochemical Staining, and expression of TGF-β1 and Col IV protein was determined by Western Blot Analyses.Results High fat diet had notable effects on the sequential levels of plasma cholesterol and triglyceride in diabetic rats. The average increase in cholesterol and triglyceride for the diabetic rats was pronounced after four weeks. This profound effect persisted for the duration of the experiment. However, high fat diet ingestion only evoked slight effects...