| Diabetic nephropathy (DN) has become a major cause of end-stage renal disease (ESRD), this is due to the facts that diabetes, particularly type 2, is increasing in prevalence and diabetes patients now live longer. It is first characterized by glomerular hemodynamic abnormalities that result in glomerular hyperfiltration, leading to glomerular damage as evidenced by microalbuminuria. As glomerular function continues to decline, overt proteinuria, decreased glomerular filtration rate, and ESRD will result. The classic pathological change in DN is the expansion of extracellular matrix in the mesangial area, with increases in types I and IV collagen and fibronectin, and decreases in proteoglycans. The pathogenesis of DN has focused on the complex interaction between genetic and hemodynamic mechanisms in addition to glycometabolic disturbance. Chronic hyperglycemia is a major initiator of DN. Due to glucose processing uses a variety of diverse metabolic pathways, hence, chronic hyperglycemia can induce multiple cellular changes leading to DN. There are several predominant well-researched theories of how hyperglycemia can produce the renal derangements that characterize diabetes. For the purposes of this review, these theories will be defined as the aldose reductase (AR) (or polyol pathway) theory, the advanced glycation end products (AGEs) theory, the reactive oxygen intermediate (ROI) theory, and the protein kinase C (PKC) theory. In recently years, AGEs are the leading investigated phenomena in DN.AGEs are generated by the sequential nonenzymatic glycation of protein amino groups and by oxidation reactions. AGEs comprise several major molecular structures, such as N-carboxymethyllysine (CML), pentosidine (PENT), vesperlysine, pyrraline and imidazolone, et al. AGEs is a common phenomenon of normal aging and occurs at an accelerated rate in patients with diabetes mellitus and in renal failure. AGEs contribute to renal injury by two major mechanisms. Firstly, the alteration of glomerular mesangiumextracellular matrix architecture and function through nonenzymatic glycation with formation of protein cross-links. Secondly, the modulation of cellular functions through interactions with specific cell surface receptors, the best characterized of which is the receptor for AGEs (RAGE).Because AGEs play an important role in the pathogenesis and progression of renal complications of diabetes, AGEs inhibitors aroused much attention in the mechanism of DN. In recent years the studies of AGEs inhibitors are restricted in the animal experiment, because of the use of nonenzymatic glycation inhibitors has disadvantages. At the present time, there isn't a safe and effective AGEs inhibitor. Chinese materia medica have extensive source, and many Chinese material medica can slow the rate of progression of DN, for this reason, the studies of Chinese materia medica inhibiting nonenzymatic glycation are become extremely importance. This study aims at investigate the effect of Bupishen Huoxue therapy on renal cortex AGEs and the expression of RAGE in diabetic rats.In the study, we performed the following experiments:1. Studies on the traditional Chinese medicine (TCM)'mechanism of DN: From the study of TCM'theoretics we conclude that the generation of DN has intimately correlation with the functional disorder of spleen and kindy. We think that the TCM'pathogenesis of incipient DN is deficiency of both vital energy and yin. The increasing of GFR and the appearance of microalbuminuria are relate with deficiency of both vital energy and yin of spleen and kindy. Hematological stagnancy play an important role in the development of DN due to hemorheological change diabetes mellitus and its complication, therefore, we advocate that to treat DN must to make use of Bupishen Huoxue therapy.2. To investigate the effectiveness of Bupishen Huoxue therapy on renal function and pathological changes in diabetic rats: Diabetic models were made by intraperitoneal injection of streptozotocin. Model group were divided into... |
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