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題 名 | Pharmacological Intervention by Exogenous Superoxide Dismutase Attenuates Diabetes-Induced Oxidative and Nitrosative Stress Mediated Renal Damage=聚乙二醇-超氧化抑制酶降低糖尿病引發氧化及硝化壓力導致的腎臟傷害 |
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作 者 | 徐永建; 董淳武; 李佩賢; 張弘育; 何正; 林俊良; | 書刊名 | 臺灣腎臟醫學會雜誌 |
卷 期 | 22:1 2008.03[民97.03] |
頁 次 | 頁20-30+75 |
分類號 | 418.2 |
關鍵詞 | 糖尿病; 氧化壓力; 硝化壓力; 超氧化抑制酶; 腎臟纖維化; 細胞凋亡; Diabetes; Oxidative stress; Nitrosative stress; Superoxide dismutase; Renal fibrosis; Apoptosis; |
語 文 | 英文(English) |
中文摘要 | 目標:本研究評估藥理上聚乙二醇-超氧化抑制酶(Superoxide dismutase, SOD-PEG)投予對糖尿病腎病變動物模型的治療效果。評估抗氧化劑介入對於oxidative stress、nitrosative stress、纖維化和細胞凋亡的影響。方法:將Streptozotocin誘導的糖尿病老鼠隨機分配為SOD-PEG和賦形劑治療的兩組。分別去量測超氧化物(O2(上標 -)、一氧化氮(NO)、IL-1β和TGF-β1的生成。腎臟則以免疫組織化學和免疫染色加以分析。結果:本研究證實了糖尿病顯著地增加了尿液中白蛋白的排出,同時也增加了糖尿病老鼠血中的超氧化物、IL-1β以及TGF-β1。有趣的是,外生性SOD-PEG的治療可以明顯地降低糖尿病的進展。在糖尿病的動物模型中,SOD的治療有效地降低了糖尿病老鼠腎臟的8-hydroxy-guandine表現,並且伴隨著TUNEL和PCNA染色的減低。進一步的研究顯示糖尿病腎臟的免疫染色有較高的peroxynitrite (OONO(上標 -))表現。外生性SOD的給予可以成功地減輕糖尿病腎臟傷害中peroxynitrite的過度表現。免疫組織化學分析顯示外生性SOD的治療可減輕TGF-β1和fibronectin的表現且降低糖尿病腎絲球中phospho-ERK和phospho-p38的表現。免疫染色則顯示可減緩nitrotyrosine、8-hydroxy-guandine、fibronectin和caspase-3蛋白在糖尿病老鼠腎臟中的表現。結論:以外生性SOD去調節氧化還原反應或許是一個提供挽救因糖尿病誘發nitrosative和oxidative傷害所造成的腎臟細胞凋亡以及纖維化的方法。 |
英文摘要 | Alias and hypothesis: This studs evaluated the rescue effect of pharmacological SOD administration on diabetic renal injury in an animal. The effect of antioxidant intervention by SOD-PEG on the indices of oxidative stress, nitrosative stress, fibrosis and apoptosis was assessed. Methods: The STZ-induced diabetic rats were randomly assigned to two groups: diabetes with SOD-PEG treatment and diabetes with vehicle treatment, Measurement of superoxide, NO, IL-1β and TGF-β1 production were carried out. Kidneys were harvested for immunohistochemical immunoblotting analysis. Results: This study demonstrated diabetes significantly increased urinary albumin excretion coinciding with increased systemic levels of superoxide IL-β and TGF-β1. Interestingly, exogenous SOD-PEG treatment significantly reduced the promotion effect of diabetes. In a diabetic animal model, SOD treatment effectively attenuated 8-hydroxy-guandine expression associated with reduced TUNEL and PCNA staining in the kidney of diabetic rats. Further studies showed higher ONOO(superscript -) expression in diabetic renal immunostaining. Exogenous SOD administration successfully lessened OONO(superscript -) over-expression in diabetic renal injury. Immunohistochemical observations showed exogenous SOD treatment attenuated TGF-β1, and fibronectin expression coincided with decreased phosphor-ERK and phosopho-p38 expression in diabetic renal glomeruli. Immunoblotting showed exogenous SOD alleviated nitrotyrosine, 8-hydroxy-guandine, fibronectin, and easpase-3 protein expression of kidney in diabetic rats. Conclusions: Ass alternative redox modulation strategy with exogenous SOD may provide a promising regimen for rescuing diabetes-promoted nitrosative and oxidative damages-related renal apoptosis and fibrosis. |
本系統中英文摘要資訊取自各篇刊載內容。