研究生: |
張瑀芳 Chang, Yu-Fang |
---|---|
論文名稱: |
消渴草減輕高脂飼料及Streptozotocin誘導第二型糖尿病大鼠主動脈損傷之研究 Alleviative Effect of Ruellia tuberosa L. on Aorta Damage in High-Fat Diet plus Streptozotocin Induced Type 2 Diabetic Rats |
指導教授: |
沈賜川
Shen, Szu-Chuan 吳瑞碧 Wu, Swi-Bea |
學位類別: |
碩士 Master |
系所名稱: |
人類發展與家庭學系 Department of Human Development and Family Studies |
論文出版年: | 2015 |
畢業學年度: | 103 |
語文別: | 中文 |
論文頁數: | 119 |
中文關鍵詞: | 第二型糖尿病 、消渴草 、主動脈損傷 |
英文關鍵詞: | Type 2 diabetes mellitus, Ruellia tuberosa L., Aorta damage |
論文種類: | 學術論文 |
相關次數: | 點閱:189 下載:11 |
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 |
第二型糖尿病 (type 2 diabetes mellitus, Type 2 DM)因胰島素阻抗 (insulin resistance) 造成高胰島素血症 (hyperinsulinemia),而高胰島素血症與高葡萄糖血症 (hyperglycemia)為糖尿病血管病變的重要影響因子。糖尿病血管病變包含大血管 (macrovascular) 及小血管 (microvascular) 病變,其中大血管病變常見為動脈粥狀硬化症,易造成患者心臟疾病的發生並導致死亡。研究指出,消渴草 (Ruellia tuberosa L.) 具有抗氧化、抗發炎、抗癌等生理活性,亦可調節糖尿病大鼠之血脂平衡。本研究首先以小鼠肌肉C2C12細胞進行細胞試驗,結果顯示,在測試濃度(25、50、100、200、400及800μg/ml)下消渴草水及乙醇萃取物皆不具有細胞毒性;接著建立以TNF-α誘導胰島素阻抗細胞模式,發現在TNF-α 10ng/ml的濃度下,可有效誘導C2C12細胞產生胰島素阻抗;之後再以此細胞模式篩選具改善胰島素阻抗潛力之消渴草萃取物,結果顯示,不論是水或乙醇之消渴草萃取物,在濃度25μg/ml下即具有改善胰島素阻抗之C2C12細胞葡萄糖攝入之能力(p<0.05)。動物試驗結果顯示,每日餵食消渴草水及乙醇萃取物(劑量100與400mg/kg BW/day) 4週後可顯著改善高脂飼料及STZ誘導第二型糖尿病大鼠葡萄糖耐受能力。血液分析的結果顯示,消渴草萃取物可調節血脂及降低發炎反應相關因子,如:TNF-α, IL-6, VCAM-1, ICAM-1的含量;組織分析結果顯示,消渴草萃取物可增加抗氧化酵素SOD的活性及catalase的活性,並且降低發炎反應相關黏附因子MCP-1, VCAM-1的含量(p<0.05)。此外,消渴草萃取物可降低血管傷害相關因子,如:eNOS, ET-1, TF, vWF的含量(p<0.05),使其恢復至正常值。
由上述結果推測,消渴草可以透過改善胰島素阻抗、發炎反應、氧化壓力等作用,而達到減輕高脂飼料及STZ誘導第二型糖尿病大鼠主動脈損傷之效果。
The diabetes mellitus patients are mainly Type 2 DM, which is characterized by hyperinsulinemia resulted from insulin resistance. Researches indicated that hyperinsulinemia and hyperglycemia are important factors in diabetic vascular disease, including macrovascular and microvascular disease. Ruellia tuberosa L. (RTL) was used as folklore medicine for diabetes in Asia as well as Taiwan. RTL was previously reported to exhibit anti-oxidant, anti-inflammatory and anti-cancer abilities. The mouse muscle myotube C2C12 cells were treated with 10ng/mL TNF-α to induce insulin resistance. These cells were subsequently co-incubated with water or ethanol extract from RTL. The uptake of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) in insulin-resistant C2C12 cells was used as a platform for screening extracts from RTL with the anti-hyperglycemic potential. The protective effect of RTL extract on aorta damage in high-fat diet plus streptozotocin induced T2DM rats was further investigated. The results show that both water and ethanol extracts from RTL (25μg/ml) significantly improves the glucose uptake in insulin-resistant C2C12 cells (p< 0.05). Both water and ethanol extracts from RTL (100 and 400mg/kg BW/day) significantly decreases plasma glucose level, decreases the concents of serum TNF-α, IL-6 and VCAM-1. The enzyme-linked immunosorbent analysis suggested that RTL decreases the contents of MCP-1, VCAM-1 and recovers the contents of eNOS, ET-1, TF and vWF in the aortas of diabetic rats.
The above observations suggested that RTL may alleviate the aorta damage via improving insulin resistance, inflammation and oxidative stress in high-fat diet plus STZ induced T2DM rats.
Abeyrathna, P., & Su, Y. (2015). The critical role of Akt in cardiovascular function. Vascular Pharmacology, doi:10.1016/j.vph.2015.05.008
Agapitov, A. V, & Haynes, W. G. (2002). Role of endothelin in cardiovascular disease. Journal of the Renin-Angiotensin-Aldosterone System, 3(1), 1–15.
Aguila, L. F. Del., Claffey, K. P., Kirwan, J. P., Aguila, D., Luis, F., Claffey, K. P., & John, P. (1999). TNF-α impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells. The American Physiological Society, 849–855.
American Diabetes Association. (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care, S81–90. doi:10.2337/dc14-S081
Ananthakrishnan M. and Aroki Doss V.. (2013) Effect of 50% Hydro-Ethanolic Leaf Extracts of Ruellia Tuberosa L. and Dipteracanthus Patulus (Jacq.) on Lipid Profile in Alloxan Induced Diabetic Rats. International Journal of Preventive Medicine; 4(7): 744-747.
Arora, A., & Dey, C. S. (2014). SIRT2 negatively regulates insulin resistance in C2C12 skeletal muscle cells. Biochemical et Biophysical Acta, 1842(9), 1372–8. doi:10.1016/j.bbadis.2014.04.027
Arun S, Giridharan P, Suthar A, Kulkarni-Almeida A, Naik V, Velmurugan R, Ram V, et al. (2008) Isolation of Tylocrebrine from Ruellia tuberosa through bioassay directed column chromatography and elucidating its anti-cancer and anti-inflammatory potential. Book of Abstracts, 7th Joint Meeting of GA, AFERP, ASP, PSI & SIF, Athens, Greece; 25.
Ashraful Alam M, Nusrat Subhan et al. (2009) Antinociceptive and anti-inflammatory properties of Ruellia tuberosa. Pharmaceutical Biology; 47(3): 209–214.
B Arirudran, A. S. and V. krishnamurthy. (2011). Evaluation of antioxidant potential of Ruellia tuberosa L . using in-vitro model. Journal of Pharmacy Research, 4(12), 4344–4347.
Balakumar, P. (2014). Implications of Fundamental Signalling Alterations in Diabetes mellitus-associated Cardiovascular Disease. Indian Journal of Biochemistry & Biophysics, 441–448.
Basili S, Pacini G, Guagnano MT, Manigrasso MR, Santilli F, Pettinella C, Ciabattoni G, Patrono C, Davi G. (2006) Insulin resistance as a determinant of platelet activation in obese women. Journal of the American College of Cardiology, 48:2531–2538.
Beckman JA, Creager MA, Libby P. (2002) Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. Journal of the American Medical Association, 287:2570–2581.
Boden G, Rao AK. (2007) Effects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of blood coagulation. Current Diabetes Reports, 7:223–227.
Busik, J. V, & Grant, M. B. (2014). Aldose reductase meets histone acetylation: a new role for an old player. Diabetes, 63(2), 402–4. doi:10.2337/db13-1696
Cavelti-Weder C, Babians-Brunner A, Keller C, Stahel MA, Kurz-Levin M, Zayed H, Solinger AM, Mandrup-Poulsen T, Dinarello CA, Donath MY. (2012) Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care, 35:1654–1662.
Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States. (2014) Atlanta, GA: U.S. Department of Health and Human Services; 2014.
Chang WC, Shen SC. (2013) Effect of water extracts from edible Myrtaceae plants on uptake of 2-(n-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose in TNF-α-treated FL83B mouse hepatocytes. Phytotherapy Research, 27(2):236-43. doi: 10.1002/ptr.4681.
Chang WC, Shen SC, Wu JS. (2013) Protective effects of vescalagin from pink wax apple [Syzygium samarangense (Blume) Merrill and Perry] fruit against methylglyoxal-induced inflammation and carbohydrate metabolic disorder in rats. Journal of Agricultural and Food Chemistry, 61(29):7102-9. doi: 10.1021/jf4020284.
Chen FA, Wu AB, Shieh P, Kuo DH, Hsieh CY. (2006) Evaluation of the antioxidant activity of Ruellia tuberosa. Food Chemistry, 94: 14–18.
Chothani, D. L., Patel, M., Mishra, S., & Vaghasiya, H. (2010). Review on Ruellia tuberosa (Cracker plant). Pharmacognosy Journal, 2(12), 506–512. doi:10.1016/S0975-3575(10)80040-9
Chwan-Fwu Lin et. al. (2006) Bioactive flavonoid from Ruellia tuberosa. J Chin Med, 17(3): 103–109.
Creager MA, Luscher TF, Cosentino F, Beckman JA. (2003) Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part I. Circulation ,108:1527–1532.
Dechend, R., Homuth, V., Wallukat, G., Kreuzer, J., Park, J. K., Theuer, J., … Luft, F. C. (2000). AT1 Receptor Agonistic Antibodies From Preeclamptic Patients Cause Vascular Cells to Express Tissue Factor. Circulation, 101(20), 2382–2387. doi:10.1161/01.CIR.101.20.2382
Dormandy, J. a, Charbonnel, B., Eckland, D. J. a, Erdmann, E., Massi-Benedetti, M., Moules, I. K., … Taton, J. (2005). Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet (London, England), 366(9493), 1279–89. doi:10.1016/S0140-6736(05)67528-9.
Drummond GR, Cai H, Davis ME, Ramasamy S, Harrison DG. (2000) Transcriptional and posttranscriptional regulation of endothelial nitric oxidesynthase expression by hydrogen peroxide. Circulation Research, 86:347–354.
Ferreira IA, Mocking AI, Feijge MA, Gorter G, van Haeften TW, Heemskerk JW, Akkerman JW. (2006) Platelet inhibition by insulin is absent in type 2 diabetes mellitus. Arteriosclerosis Thrombosis and Vascular Biology Journal 26:417–422.
Förstermann, U., & Münzel, T. (2015). Basic Science for Clinicians Endothelial Nitric Oxide Synthase in Vascular Disease. Circulation, 1708–1715. doi:10.1161/CIRCULATIONAHA.105.602532
Francesco Paneni 1,2 , Joshua A. Beckman 3 , Mark A. Creager 3 , and Francesco Cosentino.(2013) European Heart Journal, 34, 2436–2446. doi:10.1093/eurheartj/eht149.
Frankel, D. S., Meigs, J. B., Massaro, J. M., Wilson, P. W. F., Donnell, C. J. O., Agostino, R. B. D., & Tofler, G. H. (2009). Von Willebrand Factor, Type 2 Diabetes and Risk of Cardiovascular Disease: The Framingham Offspring Study. Circulation,118(24),617–624.doi:10.1161/CIRCULATIONAHA.108.792986.
Hollenberg NK. (2003)Considerations for management of fluid dynamic issues associated with thiazolidinediones. American Journal of Medicine,115(Suppl 8A):111S–115S.
Holy, E. W., & Tanner, F. C. (n.d.). Tissue Factor in Cardiovascular Disease : Pathophysiology and Pharmacological Intervention. Advances In Pharmacology Volume ,59 (Vol. 59, pp. 259–292). (Elsevier Inc.) doi:10.1016/S1054-3589(10)59009-4
Jorge Plutzky, MD, Robert S. Rosenson, MD, FACC (2012). PPARs and Cardiovascular Disease Risk Reduction in Patients with Type 2 Diabetes. CMEology, http://www.medscape.org/viewarticle/765568.
Julia V. Busik & Maria B. Grant. (2014) Aldose Reductase Meets Histone Acetylation: A New Role for an Old Player. Diabetes, 63:402–404|doi: 10.2337/db13-1696.
Kazuomi Kario, Takefumi Matsuo, Hiroko Kobayashi, Miyako Matsuo, Toshiyuki Sakata, Toshiyuki Miyata, K. S. (1996). Factor VII Hyperactivity and Endothelial Cell Damage Are Found in Elderly Hypertensives Only When Concomitant With Microalbuminuria. Arteriosclerosis, Thrombosis, and Vascular Biology, 16: 455–46.
Kersten S, Desvergne B, Wahli W. (2000) Roles of PPARs in health and disease. Nature;405:421–424.
Kim JK. (2012) Endothelial nuclear factor kappab in obesity and aging: is endothelial nuclear factor kappaB a master regulator of inflammation and insulin resistance? Circulation ;125:1081–1083.
Kushner, R. F., & Sujak, M. (2009). Prevention of weight gain in adult patients with type 2 diabetes treated with pioglitazone. Obesity (Silver Spring, Md.), 17(5), 1017–22. doi:10.1038/oby.2008.651
Lemkes BA, Hermanides J, Devries JH, Holleman F, Meijers JC, Hoekstra JB. (2010) Hyperglycemia: a prothrombotic factor? Journal of Thrombosis and Haemostasis; 8:1663–1669.
Luscher TF, Creager MA, Beckman JA, Cosentino F. (2003) Diabetes and vascular disease: pathophysiology, clinical consequences and medical therapy. Circulation ;108:1655–61.
Miller, D. L., Welty-Wolf, K., Carraway, M. S., Ezban, M., Ghio, A., Suliman, H., et al. (2002). Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide. American Journal of Respiratory Cell and Molecular Biology, 26(6), 650–658.
Miyauchi T, Goto K. Endothelins. In: Kastin Abba J, editor. Handbook of biologically active peptides. (2013) Academic Press (Elsevier Inc.); p. 1402–7.
Miyauchi, Y., Jesmin, S., Sakai, S., Kamiyama, J., Shimojo, N., & Rahman, A. (2014). Effects of selective endothelin ( ET ) -A receptor antagonist versus dual ET-A / B receptor antagonist on hearts of streptozotocin-treated diabetic rats. Life Sciences, 111(1-2), 6–11. doi:10.1016/j.lfs.2014.06.008
Naseem, K. M. (2005). The role of nitric oxide in cardiovascular diseases. Molecular Aspects of Medicine, 26, 33–65. doi:10.1016/j.mam.2004.09.003
Nissen SE, Nicholls SJ, Wolski K, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. The Journal of the American Medical Association, 2008;299(13):1561-1573.
Ohkita M, Tawa M, Kitada K, Matsumura Y. (2012) Pathophysiological roles of endothelin receptors in cardiovascular diseases. Journal of Pharmacological Sciences, 119(4):302-313
Paneni, F., Beckman, J. a, Creager, M. a, & Cosentino, F. (2013). Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. European Heart Journal, 34(31), 2436–43. doi:10.1093/eurheartj/eht149
Saltiel AR, Kahn CR. (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature ;414:799–806.
Samuel, V. T., & Shulman, G. I. (2012). Mechanisms for insulin resistance: common threads and missing links. Cell, 148(5), 852–71. doi:10.1016/j.cell.2012.02.017
Sasidharan, S. R., Joseph, J. A., Anandakumar, S., Venkatesan, V., Ariyattu Madhavan, C. N., & Agarwal, A. (2013). An experimental approach for selecting appropriate rodent diets for research studies on metabolic disorders. BioMed Research International, 752870. doi:10.1155/2013/752870
Schramm TK, Gislason GH, Køber L, Rasmussen S, Rasmussen JN, Abildstrøm SZ, et al. (2008) Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people. Circulation ;117:1945–54.
Schoonjans, K., Peinado-Onsurbe, J., Lefebvre, A. M., Hwyman, R.A., Briggs, M., Deeb, S., Auwerx, J. (1996). PPARalpha and PPARgamma activators direct adistinct tissue-specific transcriptional response via PPRE in the lipoproteiom lipase gene. The EMBO journal, 15(19), 5336-5348.
Shantikumar S, Caporali A, Emanueli C. (2012) Role of microRNAs in diabetes and its cardiovascular complications. Cardiovascular Research, 93:583–593.
Shen, S. C.,Cheng, F. C., Wu, N. J. (2008) Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats. Phytotherapy Research, 22, 1458-64.
Spiel, A. O., Gilbert, J. C., & Jilma, B. (2008). Von Willebrand Factor in Cardiovascular Disease Focus on Acute Coronary Syndromes. Circulation., 117:1449–1459. doi:10.1161/CIRCULATIONAHA.107.722827
Sun, J., Zhang, X., Broderick, M., Fein, H., Instruments, W. P., & International, S. (2003). Measurement of Nitric Oxide Production in Biological Systems by Using Griess Reaction Assay. Sensors, 276–284.
Tsimerman G, Roguin A, Bachar A, Melamed E, Brenner B, Aharon A. (2011) Involvement of microparticles in diabetic vascular complications. Journal of Thrombosis and Haemostasis, 106:310–321.
Tsunekawa, T., Hayashi, T., Kano, H., & Sumi, D. (2001). Brief Rapid Communications Reductase Inhibitor , Improves Endothelial Function in Elderly Diabetic Patients Within 3 Days. Circulation, 104:376–379.
Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors. (1999) Lancet;354:141–148.
Vazzana, N., Ranalli, P., Cuccurullo, C., & Davì, G. (2012). Diabetes mellitus and thrombosis. Thrombosis Research, 129(3), 371–7. doi:10.1016/j.thromres.2011.11.052
Verma, S., Li, S.-H., Wang, C.-H., Fedak, P. W. M., Li, R.-K., Weisel, R. D., & Mickle, D. a G. (2003). Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation, 108(6), 736–40. doi:10.1161/01.CIR.0000084503.91330.49
Yamagishi, S. I., Edelstein, D., Du, X. L., Kaneda, Y., Guzmán, M., & Brownlee, M. (2001). Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. The Journal of Biological Chemistry, 276(27), 25096–100. doi:10.1074/jbc.M007383200
Yang, M., Wei, D., Mo, C., Zhang, J., Wang, X., Han, X., Xiao, H. (2013). Saturated fatty acid palmitate-induced insulin resistance is accompanied with myotube loss and the impaired expression of health benefit myokine genes in C2C12 myotubes. Lipids in Health and Disease, 12(1), 104. doi:10.1186/1476-511X-12-104
Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. (2010) Plasma microrna profiling reveals loss of endothelial mir-126 and other microRNAs in type 2 diabetes. Circulation Research, 107:810–817.
Zampetaki A, Mayr M. (2012) MicroRNAs in vascular and metabolic disease. Circulation Research, 110:508–522.
Zheng, X., Zhu, S., Chang, S., Cao, Y., Dong, J., Li, J., Zhou, Y. (2013). Protective effects of chronic resveratrol treatment on vascular inflammatory injury in streptozotocin-induced type 2 diabetic rats: Role of NF-kappa B signaling. European Journal of Pharmacology, 720(1-3), 147–157. doi:10.1016/j.ejphar.2013.10.034
Zou, C., Wang, Y., & Shen, Z. (2005). 2-NBDG as a fluorescent indicator for direct glucose uptake measurement. Journal of Biochemical and Biophysical Methods, 64(3), 207–15. doi:10.1016/j.jbbm.2005.08.001
洪心容(2005)。台灣產九種治療糖尿病藥用植物之抗氧化及降血糖相關性之研究(碩士論文)。中國醫藥大學藥學院中國藥學研究所。
張文昌(2010)。食用桃金孃科植物萃取物減輕小鼠肝臟細胞(FL83B)胰島素阻抗之探討(碩士論文)。國立臺灣大學食品科技研究所。
張文昌(2014)。Vescalagin預防Methylglyoxal誘發大鼠醣類代謝異常之研究(博士論文)。國立臺灣大學食品科技研究所。
郭柏伶(2013)。咖啡酸對高脂飼料誘導高胰島素血症大鼠海馬迴及皮質醣類代謝之研究(碩士論文)。國立臺灣師範大學人類發展與家庭學系。
陳甄雯(2013)。香草酸對餵食高脂飼料大鼠血糖與血脂之影響(碩士論文)。國立臺灣大學食品科技研究所。
鄭勤巧(2014)。咖啡酸預防高胰島素血症大鼠阿茲海默症之機制(碩士論文)。國立臺灣師範大學人類發展與家庭學系。