三氧化二砷治療狼瘡腎炎的研發
江伯倫
國立台灣大學
全身性紅斑是全身性自體免疫疾病的主要代表疾病，主要是會產生許多自體抗體來對抗自己的組織，如紅血球、血小板、關節和腎臟等，而產生各種器官的破壞。其中最會影響到患者預後的器官便是腎臟，許多患者便是因為腎臟受到侵犯後而導致慢性腎絲球腎炎，最後甚至因為腎臟衰竭和尿毒症死亡。目前應用在全身性紅斑狼瘡的治療主要是類固醇或是一些免疫抑制劑，基本上還是會造成相當嚴重的副作用。所以開發中草藥應用到全身性紅斑狼瘡的治療，一直有相當多的研究者致力於這方面的研究。而三氧化二砷自古以來被應用到中醫應用上，雖然經由口服的方式給予時可能會導致毒性，但是利用其他方式給予時便可能有治療的效果。同時，三氧化二砷已被發現對血管的增生可能會有抑制的效果，而腎絲球發炎時也會與血管的發炎和增生有關，所以在此一計畫中將利用三氧化二砷來治療狼瘡小鼠，以了解是否可以有效地抑制自體抗體的製造，同時也達到改善腎臟發炎的情形。因此，我們將利用三氧化二砷經由腹腔內注射的方式來治療NZB/W F1小鼠，了解其可能的治療效果，尤其是針對腎臟部份的病理變化。如果治療有效時，我們將進一步研究其機轉，包括血管增生的情形，和血中相關發炎性細胞激素的濃度。經由此一動物模式的建立，可以利用來研發更多種中草藥應用到全身性紅斑狼瘡治療上的應用
關鍵字：腎炎；全身性紅斑狼瘡；三氧化二砷
Application of Arsenic Trioxide for the Treatment of Lupus Nephritis
bo-luen jiang
National Taiwan University
Key words: Systemic lupus erythematosus, arsenic trioxide, nephritis Arsenic trioxide has been used therapeutically for approximately 2,400 years, as a part of Chinese medicine. It is historically the poison and most common side effects are gastrointestinal and most inorganic arsenic after ingestion is eliminated rapidly in the urine. Arsenic trioxide has many effects on cells. It can not only induce apoptosis, but also has anti-proliferative activity. It even can inhibit angiogenesis. However, it has different mechanisms to control these effects. Arsenic trioxide may interact with targeted proteins which contain closely spaced cysteine residues. Arsenic trioxide may alter the function of several enzymes and molecules of cell signaling, such as AP-1 and result in increasing downstream molecule activity. Inflammatory signal transduction was also blocked by arsenic trioxide, which can inhibit IKK, which is required for activation of the proinflammatory transcription factor NF-kB. In therapy, arsenic trioxide is currently FDA-approved for treating chronic or acute leukemias. It is also used in clinical trials to evaluate its efficacy for treating multiple myeloma and a variety of solid tumors. In this proposal, we like to establish an animal model of lupus for the study of Chinese traditional drugs. In addition, we aimed to treat NZB/NZW F1 lupus prone mice intrperitoneally with arsenic trioxide.
關鍵字：Systemic lupus erythematosus；arsenic trioxide；nephritis
