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    题名: 三七治療小鼠肺纖維化之應用評估;The therapeutic effect of Panax notoginseng on Bleomycin-induced pulmonary fibrosis in C57BL/6 mice
    作者: 蔡昆道;Kuen-Daw Tsai
    贡献者: 中國醫藥大學中西醫結合研究所
    关键词: 肺纖維化;三七;pulmonary fibrosis;Panax notoginseng
    日期: 2004
    上传时间: 2010-01-18 11:42:55 (UTC+8)
    摘要: 三七治療小鼠肺纖維化之應用評估 中國醫藥大學中西醫結合研究所 研究生：蔡昆道 指導教授：陳光偉 肺纖維化是一種慢性發炎及漸進式間質纖維化的疾病。它廣泛侵犯肺實質的肺泡壁、間隔及血管、淋巴、氣管周圍的結締組織，而造成纖維化。病人症狀為乾咳，越來越喘及逐漸消瘦，甚至喪失工作能力，成為家庭社會的一大負擔，因此我們不得不重視此一問題。然而，造成肺纖維化的原因相當多，如SARS、其他感染、藥物、自體免疫疾病等等皆是。不過，到目前為止，大部分還是無確定原因者居多，且預後相當差，往往在診斷後5-6年即死亡。歷年來的研究發現整個疾病發展的過程中，發炎反應和間質細胞增生程度扮演很重要的角色，當某一刺激進入肺部，造成肺部表皮細胞或血管內皮的損傷，使正常結構破壞。接著是發炎反應及釋出多種調控激素，如細胞激素，化學激素及生長因子等，這些會造成纖維母細胞的轉移及增生，且分泌更多的細胞外基質，過多的細胞外基質無法清除或血管生成有問題，便逐漸發展成纖維化。肺部一旦纖維化，就無法交換氣體，以致呼吸衰竭及肺功能喪失(disability)。目前，治療肺纖維化的藥物，主要還是以類固醇為主，輔以細胞毒殺劑、免疫抑制劑或膠原合成、纖維生成激素抑制劑。但實際上，各種搭配的療效仍有限。因此，是否有其他方法可以更早期、有效的治療此疾病是當前各國醫藥界所努力的目標。中醫藥發展已有幾千年的經驗傳承，有其一定療效，唯缺乏有系統的科學化驗證。本研究將以中醫藥之理論為基礎，科學化、分階段探討中藥臨床治療肺纖維化之潛在可行性。首先找出可能具有療效或已發表關於治療纖維化的中草藥或方劑，藉由建立活體動物模型 (bleomycin-induced mice肺纖維化)的方式，針對該中草藥或方劑，評估其調控免疫系統、抑制發炎反應及抗纖維化之效果，期能經由此研究結果，提供明確療效的藥物或方劑來治療肺纖維化。本實驗以Bleomycin誘發小鼠肺纖維化，由小鼠的肺泡沖洗液 (Bronchoalveolar larvage)中測量細胞激素的變化。當處理Bleomycin的老鼠給予0.5 mg/kg/day濃度的三七，結果發現三七可藉由調控細胞激素（IL-1β, IL-6, TNF-α）及抑制TGF-β的產生而抑制小鼠肺纖維化之發展。尤其在Bleomycin處理7天後才開始給予三七的治療其療效更明顯。由小鼠肺組織切片分析之試驗結果亦得到相同的趨勢，即三七可以有效的抑制因Bleomycin誘發的小鼠肺纖維化。; Evaluation of Panax notoginseng in treating Bleomycin-induced pulmonary fibrosis in C57BL/6 mice Kun-Tao Tsai Major Professor: Guang-Wei Chen Many etiologies can induce pulmonary fibrosis such as SARS, infection, drugs or autoimmune disease ..etc. Idiopathic pulmonary fibrosis (IPF) still accounts for the most common cause. Patient with IPF has a median survival of 4 to 5 years after onset of symptoms. In reviewed literatures, we find that inflammatory response and mesenchymal proliferation play a major role in the development of pulmonary fibrosis. Once microinsults spread into lung, it will damage alveolar epithelium, vascular endothelium, and induces inflammatory response and release of many immunomodulators (cytokines, chemokines, growth factor) followed by migration, proliferation of fibroblast, excessive secretion of extracellular matrix and progression to fibrosis. If pulmonary fibrosis developed, it will result in loss of gas exchange, disability, and gradually respiratory failure. On therapy, corticosteroid is still the mainstay assisted by cytotoxic agents, inhibitors of inflammatory mediators or antioxidants. However, the efficacy of any combination is always limited. To fight this extremely contagious and fatal disease, it is urgently to find effective therapeutic agents to slow the disease progression. In the present study, an in vivo animal model (bleomycin-induced pulmonary fibrosis) for assessment of the therapeutic efficacy of certain Chinese medicine in management of pulmonary fibrosis has been established. We assessed the anti-inflammatory, immunomodulatory and anti-lung-fibrotic effects of traditional Chinese medicines for treatment of pulmonary fibrosis. We found that feeding the mice with Panax notogiseng (PN) 0.5 mg/kg/day for the 2nd day and 7th day post administration of bleomycin. Cytokines from broncho-alveolar larvage fluid were analyzed. Result showed that PN inhibited the release of bleomycin triggered pro-inflammatory cytokines (IL-1β、IL-6、TNF-α) and obviously reduced the production of TGF-β, especially in the group of mice 7th day treated with PN. These results were confirmed by Hematoxylin and Sirius Red stain. Taken together, our observations indicated that PN effectively inhibited bleomycin-induced pulmonary fibrosis in mice especially 7 days later post administering bleomycin, suggest that PN has therapeutic potency in treatment of the patients with pulmonary fibrosis.
    显示于类别:[中西醫結合研究所] 博碩士論文

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