| Summary: | 碩士 === 國立成功大學 === 環境醫學研究所 === 104 === The purpose of this study is to detect urate-lowering effects and reducing urate nephropathy mechanisms of microbial fermented extracts (MFEs) and pterostilbene (PT) by using animal and cell culture experimental models. In in vivo study, MFEs and PT hyperuricemic mice, reduced and prevented serum urate levels and liver XOD acitivity in hyperuricemic mice. In the acute toxicity study, the mice did not show any form of morbidity or mortality after gavaged MFEs. Further more, we used urate nephropathy model to confirm whether PT could prevent renal fibrosis. Our results showed that PT reduced serum urate levels and enhanced creatinine and BUN excretion in oxonate-induced hyperuricemic mice. In the kidney, HE-stained, Masson's trichrome-stained and immunohistochemistry showed PT could prevent fibrosis and EMT marker expression. Western blot analysis also demonstrated PT treatment prevent alteration in the expression of E-cadherin, Fibronectin, α-SMA and vimentin. In in vitro study, PT pretreatment could inhibite TGF-β1-induced alteration in the expression of E-cadherin, Fibronectin, α-SMA and vimentin. Moreover, PT was found to induce autophagy in NRK-52E cell, in which LC3-II expression was significantly enhanced in combined treatment with TGF-β1. Taken together, we found a new nephro-protective meachanism of PT through inhibition of TGF-β1-induced EMT by autophagy.
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