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| 題名: | 天然化合物2, 3, 5, 4′-Tetrahydroxystilbene-2-O-β-D Glucoside對於局部性腎絲球硬化症之療效評估
Therapeutic Potential of Natural Compound 2, 3, 5, 4′-Tetrahydroxystilbene-2-O-β-D Glucoside in Focal Segmental Glomerulosclerosis |
| 作者: | Bayarsengee, Uyanga |
| 貢獻者: | 臨床醫學研究所
鄭朝文 |
| 關鍵詞: | 局部性腎絲球硬化症;2、3、5、4′-Tetrahydroxystilbene-2-O-β-D Glucoside（THSG）;活化類紅血球衍生生長相關因子2（Nrf2）;腎臟保護作用
focal segmental glomerulosclerosis;THSG;Nrf2;renoprotection |
| 日期: | 2015-06-08 |
| 上傳時間: | 2020-08-11 10:13:13 (UTC+8) |
| 摘要: | Background: Focal segmental glomerulosclerosis is the worst prognosis primary glomerular diseases with progressive glomerular scarring and a clinical presentation of nephrotic syndrome in children and adults. More than half of patients with FSGS complicate end-stage renal disease (ESRD). FSGS is defined by heavy proteinuria and edema in clinical findings, but entity diagnosed by sclerotic lesions which occur part (segmental) of the glomerular capillaries in a minority (focal) of glomeruli in histological findings. Oxidative stress, depleted antioxidant ability and inflammation play most critical role in the pathogenesis. 2, 3, 5, 4′-Tetrahydroxystilbene-2-O-β-D Glucoside (THSG) is strong antioxidant compound which is extracted from Chinese traditional herbal. In this study, we evaluated these nature antioxidant compounds renoprotective effect in a mouse model of Adriamycin-induced FSGS. Furthermore, we tried to elucidate the underlying mechanisms.
Methods: In vivo study was intended for prevention. We established female BALB/C mice to induce FGSG model by AD 11mg/kg body weight, a single dose. We treated with THSG for 21 consecutive days at a daily dose of 120mg/kg body weight by oral gavage. The plasma parameters, urine protein were measured and histopathology was examined. Antioxidant enzymes and oxidative stress damage were determined in all groups. The certain fibrotic and inflammatory genes mRNA were analyzed by qPCR. In vitro study, we used CRL1927 mouse mesangial cell lines and treatment with 20μg/ml THSG.
Results: Our result support that THSG induced HO-1 expression in mesangial cell through Nrf2/Keap1 signaling pathway. THSG suppressed mesangial cell death induced by Adriamycin. We found potential effect of THSG in ameliorating proteinuria progression, improving renal function, reducing plasma total cholesterol, and enhanced catalase activity in FSGS mouse model. THSG greatly reduced certain fibrotic genes including collagen1a1, collagen4a2, tissue inhibitor of metalloproteinase and fibronectin; also certain inflammatory genes such as monocyte chemoattractant protein-1 and vascular cell adhesion molecule in FSGS mouse model.
Conclusion: The present findings indicated that THSG relieved proteinuria and kidney injury in FSGS mouse model through stimulating Nrf2/Keap1 mediated antioxidant gene expression, and suggested that THSG may be useful for prevention of oxidative stress induced kidney injury. |
| 描述: | 碩士
指導教授:鄭朝文
委員:林裕峯
委員:林景堉
委員:陳金順
委員:趙載光 |
| 資料類型: | thesis |
| 顯示於類別: | [臨床醫學研究所] 博碩士論文
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