The Effects Of High Glucose And LDL On The Accumulation Of ECM In The Tubulointerstitium In Type 2 Diabetes

Diabetic nephropathy has become the leading cause of end stage renal disease (ESRD) in United States and Europe. The percent of DN in the ESRD is also increasing significantly in our country in recent 20 years. The renal risk of type 2 diabetes is by no means less, and possibly even greater than that of type 1 diabetes. Although the glomerulus has been the focus of intense investigation in the mechanism of diabetic nephropathy in the last decades, in recent years more attention has been paid on the changes of the tubulointerstitial because the damage of tubulointerstitial is also a major feature and an important predictor of renal dysfunction both in diabetic nephropathy and others. There is no doubt that hyperglucose is the key factor of the pathogenesis in diabetic nephropathy. Hyperlipidemia has been confirmed as an another factor in the pathogenesis of DN also. Various animal models have been employed to gain more insight into the pathogenesis of nephropathy associated with type 2 diabetes. KKA~y mice are one of the best models of DN, and it has not been used in China until 1999. Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, is a kind of classic lipid-lowering agent, which has been used in many patients with nephropathy, including diabetic nephropathy. Recently, the renal protection independent of lipids regulation has been demonstrated in various animal nephropathy models, such as Dahl salt-sensitive rats, subtotal renal ablation rats. However, if lovastating has the renal protection independent of lipid lowering or not in diabetic nephropathy is still waiting to be clear. OBJECTIVES1. To study the effect of HG and LDL on the synthesis of ECM (collagen IV and FN), both on protein and nucleic acid level in vitro (KKA~y mice) and vivo conditions.