簡易檢索 / 詳目顯示

研究生: 何晉容
Ho, Ching-Jung
論文名稱: 深層海水口服與外用對於二硝基氯苯誘導之異位性皮膚炎BALB/c小鼠模式的療效
Therapeutic Effects of Oral Administration and Topical Application of Deep-Ocean-Water on DNCB-induced Atopic Dermatitis in BALB/c Mice
指導教授: 鄭劍廷
Chien, Chiang-Ting
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 75
中文關鍵詞: 皮膚炎深層海水二硝基氯苯脾臟腫大
英文關鍵詞: Dermatitis, Deep ocean water, DNCB, Splenomegaly
DOI URL: https://doi.org/10.6345/NTNU202202339
論文種類: 學術論文
相關次數: 點閱:123下載:8
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 異位性皮膚炎是一種慢性的、發炎性皮膚疾病,其病症特徵有持續性的發炎反應和有搔癢感的皮膚損傷。本研究會在BALB/c小鼠的背部皮膚上持續地使用DNCB誘發類似異位性皮膚炎病症和傷害,並且評估使用深層海水對於由DNCB處理所誘發的類似異位性皮膚炎症狀及皮膚傷害是否具有改善的效果。深層海水富含營養物質和礦物鹽,並有著抗氧化和抗發炎的特性,或許可以做為發展成新的治療方式來為皮膚提供保護,抵抗異位性皮膚炎。因為深層海水獨特的特性,在現在的研究中,認為深層海水對於DNCB誘發之類似異位性皮膚炎症狀或許有治療的潛力。本研究的結果顯示在DNCB處理的口服深層海水組別,其表皮分數和肥大細胞數量有獲得改善的效果,而且在皮下血管白血球細胞浸潤以及脾臟形態的情形有緩和的趨勢。然而,在抓癢行為、表皮增厚、脾臟腫大以及IL-4含量方面並沒有顯著性的改善。DNCB處理的口服與外用深層海水萃取物的組別,其表皮分數、表皮增厚、肥大細胞數量和IL-4含量有獲得改善的效果,而且在皮下血管白血球細胞浸潤以及脾臟形態的情形有緩和的趨勢。然而,在抓癢行為、脾臟腫大方面並沒有顯著性的改善。結論,深層海水或許在改善異位性皮膚炎是一個有潛力的治療策略,其中又以同時口服深層海水以及外用深層海水萃取物抹劑的效果最好。

    Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized with continuous inflammation and pruritic skin lesions. Repeated application of 2,4-dinitrochlorobenzene (DNCB) treated on the dorsal skin of BALB/c mice can induce AD-like symptoms and skin lesions. This study evaluated therapeutic effects of oral administration or oral combined topical application of deep ocean water (DOW) on DNCB-induced AD-like symptoms. DOW which is rich in micronutrients and minerals and with antioxidant and anti-inflammatory qualities, may be developed as an AD therapy to provide skin protection against AD. Because of the unique property of DOW, in recent studies, suggesting that its therapeutic potential on DNCB-induced AD-like symptoms in BALB/c mice.
    The present results showed that dermatitis score and number of mast cells was significantly alleviated in DNCB-treated oral administration groups, and infiltration of leukocytes and morphological changes in spleen were slightly attenuated. However, there was no significant difference in scratching behavior, epidermal thickness, splenomegaly and spleen IL-4 levels. In DNCB-treated oral administration and topical application groups, dermatitis score, epidermal thickness, number of mast cells and spleen IL-4 levels was significantly alleviated, and infiltration of leukocytes and morphological changes in spleen were slightly attenuated. However, there was no significant difference in scratching behavior and splenomegaly. In conclusion, these results suggest that DOW treatment may be a potentially therapeutic strategy in ameliorating atopic dermatitis. Furthermore, combination of oral administration and topical application of DOW had the best efficiency to ameliorate AD-like symptoms.

    目錄 1 中文摘要 4 Abstracts 6 縮寫表 8 1. 緒論 9 1-1. 異位性皮膚炎 9 1-2. 目前異位性皮膚炎的治療方式 10 1-3. 深層海水用於改善異位性皮膚炎的基本原理 11 1-4. 研究的重要性與目的 12 2. 研究材料與方法 14 2-1. 實驗動物 14 2-2. 動物分組 14 2-3. 異位性皮膚炎動物模式的誘發 15 2-4. 動物處理 16 2-5. 皮膚傷害表皮分數評估 17 2-6. 抓癢行為分析 18 2-7. 病理組織化學染色 18 2-8. 酵素免疫分析法(Enzyme-Linked ImmunoSorbent Assay) 20 2-9. 統計分析 22 3. 實驗結果 23 3-1. 深層海水有效成分分析 23 3-2. 口服深層海水後皮膚外觀改變 23 3-3. 口服深層海水後改善抓癢行為 24 3-4. 口服深層海水後皮膚病理狀態改變 26 3-5. 口服深層海水後脾臟病理狀態變化 28 3-6. 口服深層海水後IL-4含量分析 30 3-7. 口服與外用深層海水萃取物後皮膚外觀改變 30 3-8. 口服與外用深層海水萃取物後改善抓癢行為 31 3-9. 口服與外用深層海水萃取物後皮膚病理狀態改變 32 3-10. 口服與外用深層海水萃取物後脾臟病理狀態變化 34 3-11. 口服與外用深層海水萃取物後IL-4含量分析 36 4. 討論 38 5. 參考資料 44 6. 圖與表格 49 圖1、口服深層海水組別實驗設計 49 圖2、口服與外用深層海水組別實驗設計 50 圖3、深層海水有效成分分析 52 圖4、口服深層海水對於DNCB誘發的皮膚炎外觀改善情況 53 圖5、口服深層海水組別的表皮分數 54 圖6、口服深層海水小鼠抓癢行為時間量化圖 55 圖7、口服深層海水小鼠抓癢行為分數量化圖 56 圖8、小鼠背部皮膚結構圖 57 圖9、口服深層海水對於DNCB誘發的表皮增厚效果 58 圖10、口服深層海水對於DNCB誘發的紅血球堆積效果 59 圖11、口服深層海水對於DNCB誘發的白血球浸潤效果 60 圖12、口服深層海水對於DNCB誘發的肥大細胞效果 61 圖13、小鼠的體重、脾臟重量和相對重量 62 圖14、口服深層海水對於DNCB誘發的脾臟型態效果 63 圖15、口服深層海水對於脾臟IL-4含量分析 64 圖16、口服與外用深層海水萃取物對於DNCB誘發的皮膚炎外觀改善情況 65 圖17、口服與外用深層海水萃取物組別的表皮分數 66 圖18、口服與外用深層海水萃取物小鼠抓癢行為時間量化圖 67 圖19、口服與外用深層海水萃取物小鼠抓癢行為分數量化圖 68 圖20、口服與外用深層海水萃取物對於DNCB誘發的表皮增厚效果 69 圖21、口服與外用深層海水萃取物對於DNCB誘發的紅血球堆積效果 70 圖22、口服與外用深層海水萃取物對於DNCB誘發的白血球浸潤效果 71 圖23、口服與外用深層海水萃取物對於DNCB誘發的肥大細胞效果 72 圖24、小鼠的體重、脾臟重量和相對重量 73 圖25、口服與外用深層海水萃取物對於DNCB誘發的脾臟型態效果 74 圖26、口服與外用深層海水萃取物對於脾臟IL-4含量分析 75

    1. Hwang, C. Y., Chen, Y. J., Lin, M. W., Chen, T. J., Chu, S. Y., Chen, C. C., Lee, D. D., Chang, Y. T., Wang, W. J., and Liu, H. N., Prevalence of atopic dermatitis, allergic rhinitis and asthma in Taiwan: a national study 2000 to 2007. Acta Derm Venereol, 2010. 90(6): p. 589-94.

    2. Leung, D. Y., Atopic dermatitis: immunobiology and treatment with immune modulators. Clin Exp Immunol, 1997. 107 Suppl 1: p. 25-30.

    3. Bieber, T., Atopic dermatitis. N Engl J Med, 2008. 358(14): p. 1483-94.

    4. Chen, L., Martinez, O., Overbergh, L., Mathieu, C., Prabhakar, B. S., and Chan, L. S., Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an atopic dermatitis model. Clin Exp Immunol, 2004. 138(3): p. 375-87.

    5. Leung, D. Y., Boguniewicz, M., Howell, M. D., Nomura, I., and Hamid, Q. A., New insights into atopic dermatitis. J Clin Invest, 2004. 113(5): p. 651-7.

    6. Palmer, C. N., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., Goudie, D. R., Sandilands, A., Campbell, L. E., Smith, F. J., O'Regan, G. M., Watson, R. M., Cecil, J. E., Bale, S. J., Compton, J. G., DiGiovanna, J. J., Fleckman, P., Lewis-Jones, S., Arseculeratne, G., Sergeant, A., Munro, C. S., El Houate, B., McElreavey, K., Halkjaer, L. B., Bisgaard, H., Mukhopadhyay, S., and McLean, W. H., Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet, 2006. 38(4): p. 441-6.

    7. Eichenfield, L. F., Tom, W. L., Chamlin, S. L., Feldman, S. R., Hanifin, J. M., Simpson, E. L., Berger, T. G., Bergman, J. N., Cohen, D. E., Cooper, K. D., Cordoro, K. M., Davis, D. M., Krol, A., Margolis, D. J., Paller, A. S., Schwarzenberger, K., Silverman, R. A., Williams, H. C., Elmets, C. A., Block, J., Harrod, C. G., Smith Begolka, W., and Sidbury, R., Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol, 2014. 70(2): p. 338-51.

    8. Cury Martins, J., Martins, C., Aoki, V., Gois, A. F., Ishii, H. A., and da Silva, E. M., Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev, 2015(7): p. CD009864.

    9. Correa da Rosa, J., Malajian, D., Shemer, A., Rozenblit, M., Dhingra, N., Czarnowicki, T., Khattri, S., Ungar, B., Finney, R., Xu, H., Zheng, X., Estrada, Y. D., Peng, X., Suarez-Farinas, M., Krueger, J. G., and Guttman-Yassky, E., Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol, 2015. 135(3): p. 712-20.

    10. Tamagawa-Mineoka, R., Masuda, K., Ueda, S., Nakamura, N., Hotta, E., Hattori, J., Minamiyama, R., Yamazaki, A., and Katoh, N., Contact sensitivity in patients with recalcitrant atopic dermatitis. J Dermatol, 2015. 42(7): p. 720-2.

    11. Wong, V. K., Della Croce, C., Schonfeld, S., Mastrangelo, A. M., and Lebwohl, M., Use and abuse of topical corticosteroids in infections of the skin and related structures. J Drugs Dermatol, 2003. 2(3): p. 268-76.

    12. Hon, K. L., Leung, T. F., Ng, P. C., Lam, M. C., Kam, W. Y., Wong, K. Y., Lee, K. C., Sung, Y. T., Cheng, K. F., Fok, T. F., Fung, K. P., and Leung, P. C., Efficacy and tolerability of a Chinese herbal medicine concoction for treatment of atopic dermatitis: a randomized, double-blind, placebo-controlled study. Br J Dermatol, 2007. 157(2): p. 357-63.

    13. Amestejani, M., Salehi, B. S., Vasigh, M., Sobhkhiz, A., Karami, M., Alinia, H., Kamrava, S. K., Shamspour, N., Ghalehbaghi, B., and Behzadi, A. H., Vitamin D supplementation in the treatment of atopic dermatitis: a clinical trial study. J Drugs Dermatol, 2012. 11(3): p. 327-30.

    14. Bjorneboe, A., Soyland, E., Bjorneboe, G. E., Rajka, G., and Drevon, C. A., Effect of dietary supplementation with eicosapentaenoic acid in the treatment of atopic dermatitis. Br J Dermatol, 1987. 117(4): p. 463-9.

    15. de Andrade, S. C., de Carvalho, R. F., Soares, A. S., de Abreu Freitas, R. P., de Medeiros Guerra, L. M., and Vilar, M. J., Thalassotherapy for fibromyalgia: a randomized controlled trial comparing aquatic exercises in sea water and water pool. Rheumatol Int, 2008. 29(2): p. 147-52.

    16. Katsuda, S., Yasukawa, T., Nakagawa, K., Miyake, M., Yamasaki, M., Katahira, K., Mohri, M., Shimizu, T., and Hazama, A., Deep-sea water improves cardiovascular hemodynamics in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits. Biol Pharm Bull, 2008. 31(1): p. 38-44.

    17. Hwang, H. S., Kim, H. A., Lee, S. H., and Yun, J. W., Anti-obesity and antidiabetic effects of deep sea water on ob/ob mice. Mar Biotechnol (NY), 2009. 11(4): p. 531-9.

    18. Hwang, H. S., Kim, S. H., Yoo, Y. G., Chu, Y. S., Shon, Y. H., Nam, K. S., and Yun, J. W., Inhibitory effect of deep-sea water on differentiation of 3T3-L1 adipocytes. Mar Biotechnol (NY), 2009. 11(2): p. 161-8.

    19. Yokota, J., Kitaoka, T., Jobu, K., Takuma, D., Hamada, A., Onogawa, M., Yoshioka, S., Kyotani, S., and Miyamura, M., Eriobotrya japonica seed extract and deep sea water protect against indomethacin-induced gastric mucosal injury in rats. J Nat Med, 2011. 65(1): p. 9-17.

    20. asri, H., Helicobacter pylori infection and its relationship to plasma magnesium in hemodialysis patients. Bratisl Lek Listy, 2007. 108(12): p. 506-9.

    21. Yang, C. C., Yao, C. A., Lin, Y. R., Yang, J. C., and Chien, C. T., Deep-sea water containing selenium provides intestinal protection against duodenal ulcers through the upregulation of Bcl-2 and thioredoxin reductase 1. PLoS One, 2014. 9(7): p. e96006.

    22. Hataguchi, Y., Tai, H., Nakajima, H., and Kimata, H., Drinking deep-sea water restores mineral imbalance in atopic eczema/dermatitis syndrome. Eur J Clin Nutr, 2005. 59(9): p. 1093-6.

    23. Kimata, H., Tai, H., Nakagawa, K., Yokoyama, Y., Nakajima, H., and Ikegami, Y., Improvement of skin symptoms and mineral imbalance by drinking deep sea water in patients with atopic eczema/dermatitis syndrome (AEDS). Acta Medica (Hradec Kralove), 2002. 45(2): p. 83-4.

    24. Proksch, E., Nissen, H. P., Bremgartner, M., and Urquhart, C., Bathing in a magnesium-rich Dead Sea salt solution improves skin barrier function, enhances skin hydration, and reduces inflammation in atopic dry skin. Int J Dermatol, 2005. 44(2): p. 151-7.

    25. Bak, J. P., Kim, Y. M., Son, J., Kim, C. J., and Kim, E. H., Application of concentrated deep sea water inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice. BMC Complement Altern Med, 2012. 12: p. 108.

    26. Radhakrishnan, G., Yamamoto, M., Maeda, H., Nakagawa, A., KatareGopalrao, R., Okada, H., Nishimori, H., Wariishi, S., Toda, E., Ogawa, H., and Sasaguri, S., Intake of dissolved organic matter from deep seawater inhibits atherosclerosis progression. Biochem Biophys Res Commun, 2009. 387(1): p. 25-30.

    27. Fu, Z. Y., Yang, F. L., Hsu, H. W., and Lu, Y. F., Drinking deep seawater decreases serum total and low-density lipoprotein-cholesterol in hypercholesterolemic subjects. J Med Food, 2012. 15(6): p. 535-41.

    28. Kwon, H. K., Lee, C. G., So, J. S., Chae, C. S., Hwang, J. S., Sahoo, A., Nam, J. H., Rhee, J. H., Hwang, K. C., and Im, S. H., Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc Natl Acad Sci U S A, 2010. 107(5): p. 2159-64.

    29. Han, H. M., Kim, S. J., Kim, J. S., Kim, B. H., Lee, H. W., Lee, Y. T., and Kang, K. H., Ameliorative effects of Artemisia argyi Folium extract on 2,4dinitrochlorobenzeneinduced atopic dermatitislike lesions in BALB/c mice. Mol Med Rep, 2016. 14(4): p. 3206-14.

    30. Leung, D. Y., Hirsch, R. L., Schneider, L., Moody, C., Takaoka, R., Li, S. H., Meyerson, L. A., Mariam, S. G., Goldstein, G., and Hanifin, J. M., Thymopentin therapy reduces the clinical severity of atopic dermatitis. J Allergy Clin Immunol, 1990. 85(5): p. 927-33.

    31. Takano, N., Arai, I., and Kurachi, M., Analysis of the spontaneous scratching behavior by NC/Nga mice: a possible approach to evaluate antipruritics for subjects with atopic dermatitis. Eur J Pharmacol, 2003. 471(3): p. 223-8.

    32. Leung, D. Y. and Bieber, T., Atopic dermatitis. Lancet, 2003. 361(9352): p. 151-60.

    33. Brandt, E. B. and Sivaprasad, U., Th2 Cytokines and Atopic Dermatitis. J Clin Cell Immunol, 2011. 2(3).

    34. Baldo, A., Cafiero, M., Di Caterino, P., and Di Costanzo, L., Tacrolimus ointment in the management of atopic dermatitis. Clin Cosmet Investig Dermatol, 2009. 2: p. 1-7.

    35. Sohn, E. H., Jang, S. A., Lee, C. H., Jang, K. H., Kang, S. C., Park, H. J., and Pyo, S., Effects of korean red ginseng extract for the treatment of atopic dermatitis-like skin lesions in mice. J Ginseng Res, 2011. 35(4): p. 479-86.

    36. Sur, B., Lee, B., Yoon, Y. S., Lim, P., Hong, R., Yeom, M., Lee, H. S., Park, H., Shim, I., Lee, H., Jang, Y. P., and Hahm, D. H., Extract of Polygala tenuifolia Alleviates Stress-Exacerbated Atopy-Like Skin Dermatitis through the Modulation of Protein Kinase A and p38 Mitogen-Activated Protein Kinase Signaling Pathway. Int J Mol Sci, 2017. 18(1).

    37. Olsson, M., Broberg, A., Jernas, M., Carlsson, L., Rudemo, M., Suurkula, M., Svensson, P. A., and Benson, M., Increased expression of aquaporin 3 in atopic eczema. Allergy, 2006. 61(9): p. 1132-7.

    38. Weidinger, S. and Novak, N., Atopic dermatitis. Lancet, 2016. 387(10023): p. 1109-1122.

    39. Lee, S. H., Heo, Y., and Kim, Y. C., Effect of German chamomile oil application on alleviating atopic dermatitis-like immune alterations in mice. J Vet Sci, 2010. 11(1): p. 35-41.

    40. Dang, L., He, L., Wang, Y., Xiong, J., Bai, B., and Li, Y., Role of the complement anaphylatoxin C5a-receptor pathway in atopic dermatitis in mice. Mol Med Rep, 2015. 11(6): p. 4183-9.

    41. Kawakami, T., Ando, T., Kimura, M., Wilson, B. S., and Kawakami, Y., Mast cells in atopic dermatitis. Curr Opin Immunol, 2009. 21(6): p. 666-78.

    42. Chapman, J. and Bhimji, S., Splenomegaly, in StatPearls. 2017: Treasure Island (FL).

    43. Kim, C. G., Kang, M., Lee, Y. H., Min, W. G., Kim, Y. H., Kang, S. J., Song, C. H., Park, S. J., Park, J. H., Han, C. H., Lee, Y. J., and Ku, S. K., Bathing Effects of Various Seawaters on Allergic (Atopic) Dermatitis-Like Skin Lesions Induced by 2,4-Dinitrochlorobenzene in Hairless Mice. Evid Based Complement Alternat Med, 2015. 2015: p. 179185.

    下載圖示
    QR CODE