| Summary: | 碩士 === 輔仁大學 === 生命科學系碩士班 === 107 === The kidney failure caused by nephropathy is a common complication of diabetic patients and is one of the leading causes of death in many patients. In recent years, many studies have indicated that Advanced glycation end products (AGEs) and Receptor for advanced glycation end products (RAGE) are the cause of the progression of diabetic nephropathy. Not only that, acute kidney injury (AKI) caused by diabetes is one of the main causes of chronic kidney disease (CKD). In this study, the drugs we used were Hydrazine and PPAR beta/delta agonist. Hydralazine is used to treat high blood pressure and heart failure. Previous studies had pointed out that Hydralazine had the ability to prevent fibrosis in kidney failure and even reduced the performance of RAGE. PPAR β/δ is a group of nuclear receptor proteins that can regulate cell differentiation, development and metabolism. Previous studies have indicated that the activation of PPAR β/δ can effectively inhibit kidney inflammation and reduce various pro-inflammatory factors in cells. We use Hydralazine and PPAR beta/delta agonist to co-culture with AGEs and RMC cell, and observe the effects of RAGE mRNA and inflammatory factors. The results showed that RMC cells co-culture with AGEs and treated with Hydralazine and PPAR beta/delta agonist were able to reduce the mRNA of RAGE and RAGE, iNOS, COX-2 protein expression. In animal experiment, we used SD rats and continued to feed high fat diet and intraperitoneal injection of streptozotocin (STZ), followed by surgical reperfusion injury to build up acute kidney injury in diabetes rats. And then evaluated the two drugs on their RAGE mRNA ,kidney inflammation factors and the therapeutic effects of kidney failure. The results showed that Hydralazine and PPAR beta/delta agonist were able to reduce the expression of RAGE mRNA and inflammatory factors RAGE, IL-6, iNOS, COX-2 ,phosphorylated JAK2/STAT3 and reduced SOCS3 and BUN value. In summary, Hydralazine and PPAR beta/delta agonist can reduce RAGE expression and kidney inflammatory factors relatively, so it is worthwhile to conduct more in-depth research and development for this two kind of drugs to treat AKI.
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