Pathogenic Investigation and Establishment of Therapeutic Strategy in Mouse Renal Fibrosis Model

• Main Authors: YANG, SHUN-MIN, 楊舜閔
• Other Authors: CHEN, ANN
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/00763622713318490535

博士 === 國防醫學院 === 生命科學研究所 === 101 === IgA nephropathy and type II diabetes nephropathy are two of the most common types of chronic kidney disease in the world, mostly leading to renal fibrosis and uremia. The development of a therapeutic strategy remains a challenge. In the present study, we used these two nephritis models to investigate the possible mechanisms of renal inflammation and fibrosis in the kidney and thereby evaluated the effects of osthole, antroquinonol (Antroq) or thrombomodulin domain 1 (TMD1) on the development of the renal disorders. The results showed that: osthole can (1) activate NF-E2 related factor-2 (Nrf2) and its downstream pathway, (2) inhibit production of reactive oxygen species (ROS), (3) inhibit the activation of NF-kB, (4) reduce activation of the NLRP3 inflammasome, (5) inhibit apoptosis, and thus achieve the deterioration process of a mouse IgA nephropathy model; Antroqcan can (1) reduce the infiltration of mononuclear cells, (2) inhibit the generation of ROS, (3) inhibit the activation of the NLRP3 inflammation pathway in the IgA nephropathy model; TMD1 can (1) activate Nrf2 pathway, (2) suppress the generation of ROS, (3) inhibit the activation of NF-kB; (4) reduce the activation of the NLRP3 inflammation in db/db mice, a diabetic model, and TMD1 also inhibited podocyte injury and apoptosis under a high sugar environment. Our data can help elucidate the pathogenic mechanisms of renal inflammation and fibrosis, and the results may prove to be useful in the development of therapeutic strategies for chronic kidney disease.