臺灣博碩士論文加值系統

題目：黃耆對腦中風後患者疲勞之療效評估：一個隨機、雙盲、對照組的研究
研究生：劉崇祥
指導教授：謝慶良
學校暨研究所名稱：中國醫藥大學中西醫結合研究所

目的：評估黃耆(Astragalus membranaceous, AM)對腦中風後患者疲勞之療效。
方法：設計雙盲，隨機，安慰劑對照的研究方法。將64位腦中風後疲勞（poststroke fatigue, PSF）患者隨機分配到：治療組（treatment group, TG；31位）接受每日口服黃耆2.8克，為期28天，或給與相同劑量與頻率的口服安慰劑對照組（control group, CG; 33位）。主要療效指標是評估治療前後的European Organization for Research and Treatment of Cancer Quality of Life Questionaire（EORTC QLQ-C30）量表和簡式疲勞量表（Brief Fatigue Index, BFI）的評分變化。
結果：共有61位受試者（TG, 29位；CG、32位）完成試驗；比較第二次評估(visit 2)和第一次評估(visit 1)，及比較第三次評估(visit 3)和visit 1的BFI量表評分的差，TG大於CG（both p < 0.05）；visit 3和visit 1的評分差，TG的QLQ-C30量表認知功能、社會功能和整體生活品質（global quality of life）評分都大於CG（all p < 0.05）。
結論：黃耆可以提高患者的BFI評分；提高生活質量量表(EORTC QLQ-C30)中的認知功能分數、社會功能分數和整體生活品質評分
。依據我們的研究結果，建議臨床醫師應更密切關注PSF患者的醫療需求。黃耆對於PSF患者有顯著效益;未來值得擴大研究樣本數和更長時間的延伸研究。

Institution：Graduate Institute of Integrated Medicine, China Medical University, Taiwan, R.O.C.

Background：Astragalus membranaceus (AM) is the first-choice herb for fatigue treatment in traditional Chinese medicine and the main herb used for stroke treatment in China and Taiwan.The purpose of this study was to evaluate the effect of AM on poststroke fatigue (PSF).

Methods：This study was designed as a double-blind, randomized, controlled preliminary study. Sixty-four patients with PSF were assigned to treatment group (TG; 31 patients), which received oral administration of AM(2.8g three times per day) for 28 days,anda control group (CG; 33 patients), which received aplacebo.The primary outcome measureswere the changes in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30) and Brief Fatigue Index (BFI) scores.

Results：A total of 61 patients (29 patients in the TG and 32 patients in the CG) completedthe trial. The difference in BFI scores between Visit 2 and Visit 1 was –17.83 ± 17.70 in the TG, which was greater than that in the CG (–8.03 ± 9.95;p= 0.01); additionally, the difference in BFI scores between Visit 3 and Visit 1 was –16.48 ± 16.41 in the TG, which was also greater than that in the CG (–9.47 ± 13.39;p= 0.05). In the EORTC QLQ-C30, the difference in cognitive functioning scores between Visit 2 and Visit 1 was 14.37 ± 13.89 in the TG, which was greater than that in the CG (3.65 ± 19.74;p=0.02); additionally, the difference in these scores between Visit 3 and Visit 1 was 14.37 ± 16.50 in the TG, which again was greater than that in the CG (6.25 ± 19.74; p=0.04). The difference in social functioning scores between Visit 3 and Visit 1 was9.77 ± 15.12 in the TG, which was greater than that in theCG (–1.56 ± 20.46;p=0.01). The difference in global quality of life (QOL)scores between Visit 2 and Visit 1 was 14.08 ± 18.78 in the TG, which was also greater than that in the CG (1.56 ± 18.14;p=0.003); moreover, the difference in these scores between Visit 3 and Visit 1 was 10.92 ± 17.55 in the TG, and this was greater than that in the CG (1.82 ± 15.8; p=0.05).

Conclusions：AM can improve BFI scores; cognitive functioning, social functioning,and global QOL scores inthe EORTC QLQ-C30.Our results suggest thatphysicians should pay close attention to the unmet medical needsof patients with PSF. AM is helpful for treating patients with PSF; however, additional studies with a larger sample and a longer period of investigation are required.

目錄 iv
表目錄 vi
圖目錄 vii
中文摘要 1
第一章 前言 1
第二章 文獻探討 2
一、西醫方面 2
2.1 腦中風後疲勞的定義 2
2.2 PSF的盛行率 2
2.3 PSF的測量 2
2.4 PSF的原因 3
二、中醫方面 3
2.5 疲勞在中醫 3
2.5 補氣中藥 3
2.6 黃耆（AM） 3
第三章 材料與方法 5
受試者招募 5
研究設計和樣本數評估 5
AM藥物的製備 5
隨機分配程序 6
評估 7
統計分析 8
第四章 結果 9
第五章 討論 12
第六章 結論 14
參考文獻 42
Abstract 英文摘要 46
謝辭48

Fatigue after stroke. 2012. https://www.stroke.org.uk/sites/default/files/fatigue_after_stroke.pdf. Accessed 2016.
Chen, C.C., Lee, H.C., Chang, J.H., Chen, S.S., Li, T.C., Tsai, C.H., Cho, D.Y., Hsieh, C.L., 2012a. Chinese Herb Astragalus membranaceus Enhances Recovery of Hemorrhagic Stroke: Double-Blind, Placebo-Controlled, Randomized Study. Evidence-based complementary and alternative medicine : eCAM 2012, 708452.
Chen, H.W., Lin, I.H., Chen, Y.J., Chang, K.H., Wu, M.H., Su, W.H., Huang, G.C., Lai, Y.L., 2012b. A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study. Clinical and investigative medicine. Medecine clinique et experimentale 35, E1-11.
Chen, J.K., Chen, T.T., Crampton, L., 2004. Chinese medical herbology and pharmacology. Art of Medicine Press City of Industry, CA.
Colle, F., Bonan, I., Gellez Leman, M.C., Bradai, N., Yelnik, A., 2006. Fatigue after stroke. Annales de readaptation et de medecine physique : revue scientifique de la Societe francaise de reeducation fonctionnelle de readaptation et de medecine physique 49, 272-276, 361-274.
Committee, N.P., 2010. Pharmacopoeia of the People’s Republic of China. 2010 ed. Part Ⅱ. Beijing: China Medical Science Press, People’s Republic of China.
De Groot, M.H., Phillips, S.J., Eskes, G.A., 2003. Fatigue associated with stroke and other neurologic conditions: Implications for stroke rehabilitation. Archives of physical medicine and rehabilitation 84, 1714-1720.
Hao, C.Z., Wu, F., Shen, J., Lu, L., Fu, D.L., Liao, W.J., Zheng, G.Q., 2012. Clinical efficacy and safety of buyang huanwu decoction for acute ischemic stroke: a systematic review and meta-analysis of 19 randomized controlled trials. Evidence-based complementary and alternative medicine : eCAM 2012, 630124.
Knobel, H., Loge, J.H., Brenne, E., Fayers, P., Hjermstad, M.J., Kaasa, S., 2003. The validity of EORTC QLQ-C30 fatigue scale in advanced cancer patients and cancer survivors. Palliative medicine 17, 664-672.
Li, M., Qu, Y.Z., Zhao, Z.W., Wu, S.X., Liu, Y.Y., Wei, X.Y., Gao, L., Gao, G.D., 2012. Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules. Neurochemistry international 60, 458-465.
Liu, X., Kenkare, K., Li, S., Desai, V., Wong, J., Luo, X., Wood, L.J., Xu, Y., Wang, Q.M., 2015. Increased Th17/Treg Ratio in Poststroke Fatigue. Mediators of inflammation 2015, 931398.
McKechnie, F., Lewis, S., Mead, G., 2010. A pilot observational study of the association between fatigue after stroke and C-reactive protein. The journal of the Royal College of Physicians of Edinburgh 40, 9-12.
Naess, H., Waje-Andreassen, U., Thomassen, L., Nyland, H., Myhr, K.M., 2006. Health-related quality of life among young adults with ischemic stroke on long-term follow-up. Stroke; a journal of cerebral circulation 37, 1232-1236.
Ormstad, H., Aass, H.C., Amthor, K.F., Lund-Sorensen, N., Sandvik, L., 2011. Serum cytokine and glucose levels as predictors of poststroke fatigue in acute ischemic stroke patients. Journal of neurology 258, 670-676.
Pharmacy, A.C.o.C.M.a., 2004. Chinese Herbal Pharmacopeia, First ed. Department of Health, Executive Yuan, Taiwan.
Staub, F., Bogousslavsky, J., 2001. Fatigue after stroke: a major but neglected issue. Cerebrovascular diseases (Basel, Switzerland) 12, 75-81.
Tang, W.K., Lu, J.Y., Chen, Y.K., Mok, V.C., Ungvari, G.S., Wong, K.S., 2010. Is fatigue associated with short-term health-related quality of life in stroke? Archives of physical medicine and rehabilitation 91, 1511-1515.
Tyrrell, P., Smithard, D., 2005. Fatigue after stroke.
Zhang, W.J., Hufnagl, P., Binder, B.R., Wojta, J., 2003. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB activation and adhesion molecule expression. Thrombosis and haemostasis 90, 904-914.
Zhu, Z.H., Wan, H.T., Li, J.H., 2011. Chuanxiongzine-astragaloside IV decreases IL-1beta and Caspase-3 gene expressions in rat brain damaged by cerebral ischemia/reperfusion: a study of real-time quantitative PCR assay. Sheng li xue bao : [Acta physiologica Sinica] 63, 272-280.
Mead, G.E., Graham, C., Dorman, P., Slot K.B.,Lewis S.C.,, Dennis, M.S., Sandercock, P.A.G. Fatiue after stroke: baseline predictors and influence on survival. Analysis of data from UK patients recruited in the international stroke trial. PLoS ONE/www.plossone.org. march 2011/volume 6/Issue 3/e16988
Glader, E.L., Stegmayr, B., Asplund K. Poststroke fatigue: a 2-year follow-up study of stroke patients in Sweden. Stroke, 2002; 33: 1327-1333.
Winward, C., Sackley, C., Metha, Z., Rothwell, P. A population-based study of the prevalence of fatigue after transient ischemic attack and minor stroke. Stroke, 2009; 40: 757-761.
汪訒菴 編著 增批本草備要 大中國圖書公司 新北市 2002 pp.1-2.
Mead, G., Lynch, J., Greig, C., Young, A., Lewis, S., Sharpe, M. Evaluation of fatigue scales in stroke patients. Stroke, 2007; 38: 2090-2095.
Chen, H. W. et al. A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study. Clinical and investigative medicine. Medecine clinique et experimentale 35, E1-11 (2012).
LOU, X., ZHANG, B., SONG, J., LIU, B. & DENG, X. Effect of Astragalus Polysaccharide in Stimulating the Secretion of Hematopoietic 貫Growth Factors from Activated Human PBMC [J]. Traditional Chinese Drug Research & Clinical Pharmacology 5, 006 (2003).
Shao, B. M. et al. A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochemical and biophysical research communications 320, 1103-1111, doi:10.1016/j.bbrc.2004.06.065 (2004).
Wang, Y. F. et al. Protective effect of Astragalus polysaccharides on ATP binding cassette transporter A1 in THP-1 derived foam cells exposed to tumor necrosis factor-alpha. Phytotherapy research : PTR 24, 393-398, doi:10.1002/ptr.2958 (2010).
Winward, C., Sackley, C., metha, Z., Rothwell, P.M. A population-based study of the prevalence of fatigue after transient ischemic attack and minor stroke. Stroke, 2009; 40:757-761.
Glader, E.L., Stegmayr, B., Asplund, K. Poststroke fatigue a 2-year follow-up study of stroke patients in Sweden. Stroke, 2002; 33: 1327-1333.
Cleare, A.J. The HPA axis and the genesis of chronic fatigue syndrome. TRENDS in Endocrinology and Metabolism. 2004, 15(2): 55-59.
冷方南 主編 中醫証侯辨治軌範 人民衛生出版社 北京 1989 pp. 9-10.
馬子密 傅延齡 歷代本草藥性匯解 中國醫藥科技出版社 北京 2002 p. 4
馬子密 傅延齡 歷代本草藥性匯解 中國醫藥科技出版社 北京 2002 p. 684
馬子密 傅延齡 歷代本草藥性匯解 中國醫藥科技出版社 北京 2002 pp. 691-692
高木敬次郎 木村正康 漢方藥理學 南山堂 東京 1997 pp. 134-135.
王懷義 編著 醫林改錯發揮 山西科學技術出版社 太原 1999 pp. 92-94.
汪訒菴 編著 醫方集解 大孚書局 台南市 1994 pp..21-22。
Li, M., Qu, Y.Z., Zgao, Z.W., Wu, S.X., Liu, Y.Y., Wei, X.Y., Gao, L., Gao, G.D. Astrgaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules. Neurochemistry International, 2012, 60: 458-465.
Zgang, W.J., Hufnag, P., Binder, B.R., Wojta, J. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-κB activation and adhesion molecule expression. Thromb Haemost, 2003; 90: 904-914.