| Objective:Diabetic nephropathy(DN) has already been one of the main etiological factors of end stage of renal failure because the diabetes mellitus'morbidity rises year by year in China.The patients with DN have to live by dialysis or a kidney transplant at last,which results in the great financial consumption and severe individual depression.To prevent and cure DN is the nephrologists' crucial duty. Lipoprotein(a) is an special type of low-density lipoprotein(LDL) that has been learnt at first by Berg, an Norwegian geneticist. It consists of characteristic apolipoprotein(a) which contains a long repeated chain of a structure found in plasminogen called Kringle 4(Kringle because of its supposed resemblance to a pastry,like a pretzel).Therefore, Lipoprotein(a) can inhibit competitively plasminogen from being activated.Microangiopathy,the important pathological background of DN,consists of microvascular endothelial injury, basilar membrane thickening, arteriosclerosis, abnormal coagulability of blood,vascular emphraxis and so on.Certainly,the inhibited fibrinolytic function will aggravate renal lesion.In theseyears,the elevated level of lipoprotein(a) corresponding to chronic microangiopathy has been found in diabetic patients. In order to investigate the role that lipoprotein(a) plays in DN progress,the relationship among the levels of serum lipoprotein(a),fibrinolytic function and the extent of nephropathy progress was studied from the experimental and clinical angles.In addition,how fluvastatin alleviates the renal lesion was analyzed through the meddling trials in diabetic rats and the patients of type 2 DN.Ultimately,the theoretic basement was advanced for preventing and curing human DN.Methods: In the animal experiment,male Sprague-Dawley rats weighting 180-220 g were made diabetes mellitus by a single celioinjection of streptozotocin (STZ) bought from Sigma(65mg/kg body weight) in 0. Immol/L citrate buffer(pH 4.5).Rats receiving an injection of citrate buffer were used as controls.The levels of blood glucose were determined 2 days after the injection of STZ or vehicle,and rats with blood glucose levels ^16.65 mmol/L were used as diabetic rats.These rats were divided into 3 groups: diabetic rats(Group DC), diabetic rats treated with fluvastatin (2mg/kg body weight everyday, Group DF) and control rats (Group NC).A11 rats were allowed free access to food and water. 2 weeks and also 6 weeks after the treatment with fluvastatin,the following studies were performed in every group. All of the items such as body weight,kidney weight,theamount of 24 hours urine,serum lipids consisting of total cholesterol ( TC ), triglyceride (TG), high-density lipoprotein (HDL-C), lipoprotein (a),blood glucose(BG), serum creatinine (Scr),urine creatinine and urine albumin excretory rate(UAER) were measured.The index about kidney hyertrophy(ratio of kidney weight to body weight) and creatinine clearance rate corrected by body weight(Ccr) were calculated. Immunohistochemical technique was used to estimate the expression of type IV collagen and laminin in renal cortex and the results were analyzed semi-quantitatively with the pathological image analysis system.The renal tissue of diabetic rats was observed with light microscope after periodic acid-Schiff( PAS) staining and transmission electron microscope.In the clinical trial,after excluding the patients with proteinuria resulted from cardiopathy, hepatopathy and primary nephropathy,80 type 2 diabetic patients with continuous microalbuminuria(20 u g/min |
PDF Full Text Request