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研究生(外文):Fang Yu Chen
論文名稱(外文):Immunomodulation of Longdan-Xiegan-Tang on CD4+CD25+ T Cell in MRL lpr/lpr Mice
指導教授(外文):T. Y. Lee
外文關鍵詞:Longdan Xiegan TangCD4+CD25+ T cellsystemic lupus erythematosusAntioxidants
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龍膽瀉肝湯是中醫臨床最常用的清熱瀉火劑之一。過去研究發現中藥方劑龍膽瀉肝湯具有抗發炎、保肝及免疫刺激等效用。在本實驗中,以MRL lpr/lpr小鼠為自發性自體免疫疾病動物模式,小鼠在生長的過程中會出現類似人類全身性紅斑性狼瘡的症狀,探討MRL lpr/lpr小鼠給予龍膽瀉肝湯餵食後出現的生理反應。於第19週大隨機分組,實驗組小鼠給予龍膽瀉肝湯(250mg/kg) ,每天一次經由胃管連續餵食二週。收集血液、脾臟與腎臟組織進行病理檢驗與免疫分析。實驗結果發現,MRL lpr/lpr小鼠呈現明顯脾臟腫大的現象,龍膽瀉肝湯治療組的小鼠脾臟明顯縮小,我們分析這作用與脾臟中CD3+CD4+、CD3+CD8+及CD4+CD25+T細胞的增加情形有關。龍膽瀉肝湯介入MRL lpr/lpr小鼠治療,顯著降低血中Anti-dsDNA、TNF-α與IFN-γ的濃度,並可增加腎臟組織內GSH的含量及減少iNOS及COX-2蛋白質表現,進而降低MRL lpr/lpr小鼠體內的氧化壓力及緩解發炎情形,也確實改善了MRL lpr/lpr小鼠外觀脫毛潰爛發炎的現象。龍膽瀉肝湯也改善MRL lpr/lpr小鼠嚴重的腎膈增生情形,腎臟組織IgG染色沉積也較MRL組輕微。蛋白質體研究結果發現,龍膽瀉肝湯對於緩解MRL lpr/lpr小鼠疾病嚴重度可能是透過增加腎臟組織裡的phosphoglycerate kinase 1蛋白質的表現並降低ferritin light chain 1、selenium-binding protein 2及alpha-enolase等蛋白質的表現。
Longdan Xiegan Tang (LXT) is a Chinese herbal medicine that is prescribed as an anti-inflammatory aid, a hepato-protectant, and an immunostimulant. In this study, we examined the biological effects of LXT administration in MRL/lpr mice.
MRL/lpr mice develop immunological disturbances and deregulated production of Th1 and Th2 cytokines and are a good model of systemic lupus erythematosus (SLE). Female MRL/lpr mice were randomly separated into two groups. The experimental group received LXT (250 mg/kg/day, po) from 19 to 21 weeks of age. At 21 weeks of age, the animals were euthanized and kidneys and spleens were removed for evaluation. Splenic CD3+CD4+, CD3+CD8+, and CD4+CD25+ T cells were increased in the LXT-administered mice compared to MRL/lpr controls, and this was associated with splenomegaly.
There was a marked reduction in IFN-, TNF-, anti-dsDNA antibody, and there were reduced IgG immune complex deposits in the glomeruli. LXT also restored kidney glutathione levels, thereby limiting the toxic effects of the inflammatory mediators iNOS and COX-2, which are overproduced in MRL/lpr mice. Two-dimensional gel electrophoresis was used to analyze proteome changes. LXT protected MRL/lpr mice against developing the lupus syndrome through up-regulation of phosphoglycerate kinase 1 and down-regulation of ferritin light chain 1, selenium-binding protein 2, and alpha-enolase, which were identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry.
This study indicates that LXT at this dose and time course of administration was effective in reducing oxidative stress associated with disease progression in MRL/lpr mice. LXT could be useful as adjunctive therapy for reducing distress in SLE.
中文摘要 I
縮寫對照表 IV
目錄 VI
第一章緒論 1
第二章 研究目的 25
第三章 實驗材料和方法 26
第四章 結果 41
第五章 討論 44
第六章 結論 49
參考文獻 50
圖表附錄 63
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