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標題: | γ-胺基丁酸對von Hippel-Lindau缺失腎損傷模式的神經與免疫反應調控 Gamma-Aminobutyric Acid Modulates Neuronal and Immune Regulation in the von Hippel-Lindau Deficient Model of Renal Injury |
作者: | 林雅莉 Alana Jr Ang Barretto |
指導教授: | 林璧鳳 Bi-Fong Lin |
關鍵字: | γ-胺基丁酸,發炎,神經生長,VHL,細胞激素, Gamma-aminobutyric acid,inflammation,nerve growth,VHL,cytokines, |
出版年 : | 2024 |
學位: | 碩士 |
摘要: | 抑制性神經傳導物質γ-胺基丁酸(GABA)已被證明能夠緩解腎小管特定條件von Hippel-Lindau(VHL)基因敲除小鼠(Hoxb7-Cre-GFP/+; Vhlhfl/fl)或(Vhlhfl/fl)的腎臟發炎並增加壽命,這些小鼠自發性地發展出發炎和腎臟損傷。 這促使人們對神經抑制與免疫反應之間的相關性進行研究。
為了研究神經抑制與免疫反應之間的關係,將Vhlhfl/fl小鼠與野生型小鼠(Hoxb7-Cre-GFP/+; Vhlh+/fl or Hoxb7-GFP/-; Vhlhfl/fl 小鼠)進行比較 ,並在為期10週的時間裡餵食含有79.5g/kg GABA補充劑的AIN-93飲食。實驗中我們透過免疫組織化學染色法來觀察了腎臟神經形態。在動物模型的脾臟以及HEK-293和HK-2細胞系中,使用shVHL25和shVHL61基因敲除來評估發炎因子,這些基因以0 μM、250 μM以及500 μM 的 GABA來進行處理.。 數據顯示,VHL缺陷的動物以及細胞導致了他們的抗發炎細胞因子(IL-6, TNF-α, IFN-γ, IL-17A/F, TGF-β, and MCP-1) 、VHL 症狀標記 (HIF, EPO, and VEGF) 以及神經營養因子 (NGF and BDNF)的表現上升。然而GABA的補充都會導致抗發炎細胞因子、VHL症候標記以及神經營養因子的表現下降。值得注意的是,接受GABA處理的組別也表現出神經生長的減少,顯示GABA可能透過抑制神經生長來對抗腎臟損傷。該研究顯示了GABA在調節腎臟損傷背景下的免疫反應和神經調控方面的治療潛力。 The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) was shown to alleviate renal inflammation and increase lifespan of the renal tubule specific condition von Hippel-Lindau (VHL) gene knockout mice (Hoxb7-Cre-GFP/+; Vhlhfl/fl) or (Vhlhfl/fl) that spontaneously develop inflammation, and renal injury. Prompting investigations into the correlations between the neuronal inhibition and the immune response. To study the correlation between neuronal inhibition and the immune response, Vhlhfl/fl mice were compared to the wild-type (Hoxb7-Cre-GFP/+; Vhlh+/fl or Hoxb7-GFP/-; Vhlhfl/fl mice) and fed AIN-93 diets containing 79.5g/kg of GABA supplementation for a 10-week period. Renal nerve morphology was assessed through 3-dimensional immunohistochemistry staining. Inflammatory factors were assessed in the spleen of the animal model as well as in vitro with the use of HEK-293 and HK-2 cell lines, featuring shVHL25 and shVHL61 gene knockdowns, that were treated with 0 μM, 250 μM, and 500 μM of GABA. Our data showed that VHL deficit animal and cell models resulted in an increase of pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, IL-17A/F, TGF-β, and MCP-1), VHL syndrome markers (HIF, EPO, and VEGF) and neurotropic factors (NGF and BDNF). Indicating the inflammatory response and early markers of angiogenesis. However, GABA supplementation resulted in a downregulation of this response. Notably, GABA-treated groups also exhibited a decrease in nerve growth, suggesting a potential mechanism through which GABA may confer protective effects against renal injury by suppressing nerve growth. This study underscores the therapeutic potential of GABA in modulating neuronal and immune regulation in renal injury. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/92369 |
DOI: | 10.6342/NTU202400126 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 生化科技學系 |
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