The Study Of Protective Effect And Mechanism Of Curcumin On Kidney Of Diabetic Rats

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus (DM). Many patients with DM are predisposed to developing diabetic nephropathy and die from it. and it is now the single commonest cause of end-stage renal failure in industrialized country such as America, our country also has this trend. Up to now, the pathophysiological mechanism responsible for DN has not been fully understood and DN hasn't been treated well yet. It seems to occur as a result of the interaction of metabolic and haemodynamic factors. Hyperglycemia and lipid abnormalities are the essential cause contributed to DN. Glucose dependent pathway includes renal polyol formation,nonenzymatic reactions between sugars and the free amino groups on proteins, lipids, and nucleic acids and the formation of advanced glycation end products (AGEs), activation of Protein Kinase C, oxidative stress, and so on. Increasing expression of cytokine especially TGF-beta 1, abnormality of cell cycle and apoptosis also play important role in the development of DN. So it is of great significance to study the mechanism of DN and find effective drugs for treatment . Curcumin, the yellow curry pigment isolated from turmeric powder, is known to have many effect, such as hypolipidemic, antioxidant, scavenging free radicals, anti-inflammatory, anti-tumor, anti-microbial, and so on. In India, turmeric(Curcuma longa) is used to treat DM, Suresh Babu reported dietary curcumin might ameliorate renal lesion associared with diabetes in streptozotocin diabetic rats, but the similar report is few and the mechanism has not been reported yet. So further studying the protective effect and mechanism of curcumin on kidney of diabetes is to be worth. The purpose of this study was to investigate the influence and mechanisms of curcumin to kidney in diabetic rats induced by streptozotocin (STZ), so as to provide experimemtal evidence for its use in clinic to treat DN. In the present study, we induced diabetic model by a single intraperitoneal injection of streptozoticin(STZ) to male Wistar rats, curcumin was given at a dose of 200mg·kg-1·day-1 by perfusing stomach for 8 weeks. Then observed the effect of curcumin on renal lesion, the mechanism was also studied. The whole experimemt could be divided into five parts. 1) To observe the protective effect of curcumin on kidney of diabetic rats. 2)To observe the effect of curcumin on glucose and lipid metabolism and oxidative stress in diabetic rats. 3) To investigate the effect of curcumin on the formation of advanced glycation end products(AGEs) and the expression of receptor for advanced glycation end products(RAGE) mRNA in renal cortex of diabetic rats by fluorescence and RT-PCR respectively. 4) To investigate the effect of curcumin on the expression of transforming growth factor-beta 1(TGF-beta 1) and its receptor RⅠ,RⅡ in kidney of diabetic rats from both gene and protein level by RT-PCR and Immunohistochemistry respectively. 5) To investigate the effect of curcumin on the expression of connective tissue growth factor(CTGF) in kidney of diabetic rats from both gene and protein level by RT-PCR and Immunohistochemistry respectively. Main results and conclusions are as followed: 1. Curcumin has protective effect on kidney of diabetic rats. It might ameliorate kidney hypertrophy and hyperfiltration, decrease urinaryalbumin, improve renal pathological damage and retard the progression of DN. 2. Curcumin can effectively correct the disorder of lipid metabolism and inhibit oxidative stress in diabetic rats, but have little effect on glucose metabolism. These levels of serum TC, TG and LDL-C were all significantly decreased in curcumin-treated diabetic rats as compared with non curcumin-treated diabetic rats, while the level of HDL-C was higher than that in non curcumin-treated diabetic rats; these activities of SOD and CAT in serum and renal cortex were higher and MDA level was lower in curcumin-treated diabetic rats than those in non curcumin-treated diabetic rats. As for levels of BG and H...