| Summary: | 碩士 === 國立交通大學 === 生物科技學系 === 105 === Diabetic nephropathy is a common complication of diabetes and is the primary cause of end-stage Renal Disease worldwide. The following uremia accounts for the increasing amount of hemodialysis population. Approximately 20% to 30% of all diabetics will develop diabetic nephropathy. Type 1 diabetes will become overt nephropathy after 10 to 15 years and get 50% chance to result in ESRD. However, there is about 30% of type 2 diabetes progressing to overt nephropathy and then just 20% develop ESRD after 20 years. According to Annual Data Report presents data on end–stage renal disease, in addition to the highest incidence of diabetic nephropathy in Taiwan, the prevalence of it ranks second in the world. This makes diabetic nephropathy occupy the fifth leading causes of deaths in Taiwan. Thus, it is urgent issue to find the efficient therapy to preventive intervention.
Hyperglycemia in diabetic patients promoted the production of AGEs, so that AGEs stimulated cells to generate harmful ROS and secrete proinflammatory cytokines, which damaged endothelial cells and recruited macrophages. Then, releasing tissue factors by macrophages resulted in glomerular basement membrane(GBM) thickening, mesangial expansion, renal coagulation and so on. Rosmarinic acid had been reported to possess a range of biological activities such as anti-inflammation, antioxidant and antifibrosis. In addition, IL-10 expression up-regulated by rosmarinic acid could inhibit macrophages secreting tissue factor. Therefore, in order to investigate whether rosmarinic acid ameliorated diabetic nephropathy through inhibiting Monocyte tissue factor expression and found out the possible signaling pathway, we injected streptozotocin (50mg/kg) in C57BL/6 mice to induce diabetic nephropathy as our animal model; meanwhile, we chose LPS-induced RAW264.7 cell line to establish our cell model.
Our data showed that rosmarinic acid not only inhibited LPS-induced RAW264.7 expressing tissue factor and inflammatory cytokines, but also transformed M1 phenotype into M2 phenotype. Treatment with RA recovered body weight, decreased blood glucose concentration and reduced urine excretion in STZ-DN mice. Section observation indicated that RA is able to improve GBM thickening, moderate mesangial expansion, regulate macrophage recruitment and decrease renal fibrosis. Consequently, our studies showed that RA ameliorated the inflammatory response and fibrosis to protect kidney from the development of diabetic nephropathy.
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