| Summary: | 碩士 === 國防醫學院 === 微生物及免疫學研究所 === 100 === Membranous nephropathy (MN), an autoimmune glomerulonephritis characterized by accumulation of immune-complexes deposit on the outter aspect of the glomerular basement membrane, is one of the most common causes of idiopathic nephrotic syndrome in adults. The deposited immune complexes and sequentially responses including inflammations, complement activations, and oxidative injuries participated in the pathogenesis of MN. Presently available immunosuppressive therapies are not always effective and have many side effects. Therefore, the ideal agents for MN treatment remains are ill-defined. Melatonin (N-acetyl-5-methoxytryptamine) is the major secretory hormone produced by pineal gland and displays multifunctional properties. It regulates various physiological functions including circadian and seasonal rhythms. In addition, melatonin exerts powerful antioxidant and anti-inflammatory properties. Therefore, we design this project to investigate the therapeutic effects and mechanisms of melatonin in murine MN model induced by cationic bovine serum albumin. Each mouse will receive melatonin or PBS by subcutaneously injections daily. The result revealed that MN mice treated with high dosage melatonin displayed a significant reduction in proteinuria and attenuated immune-complexes deposition in kidneys. The CD19+ B-cell subpopulation was also significantly reduced in the MN mice treated with melatonin. Expression of cytokine mRNAs in splenocytes showed that melatonin reduced the expression of proinflammatory cytokines and increased the expression of anti-inflammatory cytokines. Melatonin treatment also up-regulated heme oxygenase-1 (HO1) expression in mice. The production of reactive oxygen species and TUNEL-positive apoptotic cells in the kidney were also significantly reduced in the melatonin-treated MN mice. Furthermore, blocking HO1 using SnPP, a HO1 inhibitor, mitigated the renoprotective effects of melatonin during MN treatment. Together, our results suggest that melatonin enhances endogenous HO1 and represses immune responses to ameliorate experimental murine MN. Melatonin should be considered a potential therapeutic intervention for MN in the future.
|
|---|
