請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71068完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 呂紹俊 | |
| dc.contributor.author | Juo-Hsiang Pai | en |
| dc.contributor.author | 白若湘 | zh_TW |
| dc.date.accessioned | 2021-06-17T04:51:20Z | - |
| dc.date.available | 2020-10-09 | |
| dc.date.copyright | 2018-10-09 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-07-31 | |
| dc.identifier.citation | Ait-Oufella, H., Taleb, S., Mallat, Z., and Tedgui, A. (2011). Recent advances on the role of cytokines in atherosclerosis. Arterioscler Thromb Vasc Biol 31, 969-979. Anstee, Q.M., Targher, G., and Day, C.P. (2013). Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 10, 330-344. Antonopoulos, A.S., Margaritis, M., Lee, R., Channon, K., and Antoniades, C. (2012). Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials. Curr Pharm Des 18, 1519-1530. Bancells, C., Canals, F., Benitez, S., Colome, N., Julve, J., Ordonez-Llanos, J., and Sanchez-Quesada, J.L. (2010a). Proteomic analysis of electronegative low-density lipoprotein. J Lipid Res 51, 3508-3515. Bancells, C., Sanchez-Quesada, J.L., Birkelund, R., Ordonez-Llanos, J., and Benitez, S. (2010b). HDL and electronegative LDL exchange anti- and pro-inflammatory properties. J Lipid Res 51, 2947-2956. Bechor, S., Zolberg Relevy, N., Harari, A., Almog, T., Kamari, Y., Ben-Amotz, A., Harats, D., and Shaish, A. (2016). 9-cis beta-Carotene Increased Cholesterol Efflux to HDL in Macrophages. Nutrients 8, 1-13. Benitez, S., Bancells, C., Ordonez-Llanos, J., and Sanchez-Quesada, J.L. (2007). Pro-inflammatory action of LDL(-) on mononuclear cells is counteracted by increased IL10 production. Biochim Biophys Acta 1771, 613-622. Benitez, S., Camacho, M., Arcelus, R., Vila, L., Bancells, C., Ordonez-Llanos, J., and Sanchez-Quesada, J.L. (2004). Increased lysophosphatidylcholine and non-esterified fatty acid content in LDL induces chemokine release in endothelial cells. Relationship with electronegative LDL. Atherosclerosis 177, 299-305. Bhatnagar, D., Soran, H., and Durrington, P.N. (2008). Hypercholesterolaemia and its management. BMJ 337, a993. Brereton, C.F., Sutton, C.E., Lalor, S.J., Lavelle, E.C., and Mills, K.H. (2009). Inhibition of ERK MAPK suppresses IL-23- and IL-1-driven IL-17 production and attenuates autoimmune disease. J Immunol 183, 1715-1723. Calzadilla Bertot, L., and Adams, L.A. (2016). The Natural Course of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 17, 1-13. Chan, K.F., Siegel, M.R., and Lenardo, J.M. (2000). Signaling by the TNF receptor superfamily and T cell homeostasis. Immunity 13, 419-422. Chen, C.H., Jiang, T., Yang, J.H., Jiang, W., Lu, J., Marathe, G.K., Pownall, H.J., Ballantyne, C.M., McIntyre, T.M., Henry, P.D., et al. (2003). Low-density lipoprotein in hypercholesterolemic human plasma induces vascular endothelial cell apoptosis by inhibiting fibroblast growth factor 2 transcription. Circulation 107, 2102-2108. Chistiakov, D.A., Melnichenko, A.A., Myasoedova, V.A., Grechko, A.V., and Orekhov, A.N. (2017). Mechanisms of foam cell formation in atherosclerosis. J Mol Med (Berl) 95, 1153-1165. Chistiakov, D.A., Orekhov, A.N., and Bobryshev, Y.V. (2015). Endothelial Barrier and Its Abnormalities in Cardiovascular Disease. Front Physiol 6, 365. Chu, E.M., Tai, D.C., Beer, J.L., and Hill, J.S. (2013). Macrophage heterogeneity and cholesterol homeostasis: classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL. Biochim Biophys Acta 1831, 378-386. Cohen, J.C., Horton, J.D., and Hobbs, H.H. (2011). Human fatty liver disease: old questions and new insights. Science 332, 1519-1523. Corr, E.M., Cunningham, C.C., and Dunne, A. (2016). Cholesterol crystals activate Syk and PI3 kinase in human macrophages and dendritic cells. Atherosclerosis 251, 197-205. Dai, X.Y., Cai, Y., Mao, D.D., Qi, Y.F., Tang, C., Xu, Q., Zhu, Y., Xu, M.J., and Wang, X. (2012). Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice. J Mol Cell Cardiol 53, 509-520. De Castellarnau, C., Sanchez-Quesada, J.L., Benitez, S., Rosa, R., Caveda, L., Vila, L., and Ordonez-Llanos, J. (2000). Electronegative LDL from normolipemic subjects induces IL-8 and monocyte chemotactic protein secretion by human endothelial cells. Arterioscler Thromb Vasc Biol 20, 2281-2287. De la Paz Sanchez-Martinez, M., Blanco-Favela, F., Mora-Ruiz, M.D., Chavez-Rueda, A.K., Bernabe-Garcia, M., and Chavez-Sanchez, L. (2017). IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein. Lipids Health Dis 16, 196. Estruch, M., Sanchez-Quesada, J.L., Beloki, L., Ordonez-Llanos, J., and Benitez, S. (2013). The Induction of Cytokine Release in Monocytes by Electronegative Low-Density Lipoprotein (LDL) Is Related to Its Higher Ceramide Content than Native LDL. Int J Mol Sci 14, 2601-2616. Favari, E., Chroni, A., Tietge, U.J., Zanotti, I., Escola-Gil, J.C., and Bernini, F. (2015). Cholesterol efflux and reverse cholesterol transport. Handb Exp Pharmacol 224, 181-206. Geloen, A., Helin, L., Geeraert, B., Malaud, E., Holvoet, P., and Marguerie, G. (2012). CD36 inhibitors reduce postprandial hypertriglyceridemia and protect against diabetic dyslipidemia and atherosclerosis. PLoS One 7, e37633. Goldstein, J.L., and Brown, M.S. (1977). The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 46, 897-930. Handberg, A., Hojlund, K., Gastaldelli, A., Flyvbjerg, A., Dekker, J.M., Petrie, J., Piatti, P., Beck-Nielsen, H., and Investigators, R. (2012). Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population. J Intern Med 271, 294-304. Hashizume, M., and Mihara, M. (2012). Atherogenic effects of TNF-alpha and IL-6 via up-regulation of scavenger receptors. Cytokine 58, 424-430. Hsu, J.F., Chou, T.C., Lu, J., Chen, S.H., Chen, F.Y., Chen, C.C., Chen, J.L., Elayda, M., Ballantyne, C.M., Shayani, S., et al. (2014). Low-density lipoprotein electronegativity is a novel cardiometabolic risk factor. PLoS One 9, e107340. Ishino, S., Mukai, T., Kume, N., Asano, D., Ogawa, M., Kuge, Y., Minami, M., Kita, T., Shiomi, M., and Saji, H. (2007). Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with atherosclerotic plaque instability--analysis in hypercholesterolemic rabbits. Atherosclerosis 195, 48-56. Itabe, H., Obama, T., and Kato, R. (2011). The Dynamics of Oxidized LDL during Atherogenesis. J Lipids 2011, 418313. Jager, R., Lowery, R.P., Calvanese, A.V., Joy, J.M., Purpura, M., and Wilson, J.M. (2014). Comparative absorption of curcumin formulations. Nutr J 13, 11. Kakutani, M., Ueda, M., Naruko, T., Masaki, T., and Sawamura, T. (2001). Accumulation of LOX-1 ligand in plasma and atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits: identification by a novel enzyme immunoassay. Biochem Biophys Res Commun 282, 180-185. Kataoka, H., Kume, N., Miyamoto, S., Minami, M., Morimoto, M., Hayashida, K., Hashimoto, N., and Kita, T. (2001). Oxidized LDL modulates Bax/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 21, 955-960. Kataoka, H., Kume, N., Miyamoto, S., Minami, M., Moriwaki, H., Murase, T., Sawamura, T., Masaki, T., Hashimoto, N., and Kita, T. (1999). Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions. Circulation 99, 3110-3117. Ke, L.Y., Engler, D.A., Lu, J., Matsunami, R.K., Chan, H.C., Wang, G.J., Yang, C.Y., Chang, J.G., and Chen, C.H. (2011). Chemical composition-oriented receptor selectivity of L5, a naturally occurring atherogenic low-density lipoprotein. Pure Appl Chem 83. Kim, D., Kim, W.R., Kim, H.J., and Therneau, T.M. (2013). Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 57, 1357-1365. Kume, N., Moriwaki, H., Kataoka, H., Minami, M., Murase, T., Sawamura, T., Masaki, T., and Kita, T. (2000). Inducible expression of LOX-1, a novel receptor for oxidized LDL, in macrophages and vascular smooth muscle cells. Ann N Y Acad Sci 902, 323-327. Lai, Y.S., Yang, T.C., Chang, P.Y., Chang, S.F., Ho, S.L., Chen, H.L., and Lu, S.C. (2016). Electronegative LDL is linked to high-fat, high-cholesterol diet-induced nonalcoholic steatohepatitis in hamsters. J Nutr Biochem 30, 44-52. Levitan, I., Volkov, S., and Subbaiah, P.V. (2010). Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxid Redox Signal 13, 39-75. Li, L., Sawamura, T., and Renier, G. (2004). Glucose enhances human macrophage LOX-1 expression: role for LOX-1 in glucose-induced macrophage foam cell formation. Circ Res 94, 892-901. Liang, C.W., Lai, Y.C. and Chu, Y.H. (2004). A study of the effects of nine chinese herbs on proinflammatory cytokines production in two cell culture models. J.Chin Med 15: 293-304. Libby, P., Ridker, P.M., and Hansson, G.K. (2011). Progress and challenges in translating the biology of atherosclerosis. Nature 473, 317-325. Libby, P., Ridker, P.M., and Maseri, A. (2002). Inflammation and atherosclerosis. Circulation 105, 1135-1143. Liu, W., Yin, Y., Zhou, Z., He, M., and Dai, Y. (2014). OxLDL-induced IL-1 beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation. Inflamm Res 63, 33-43. Loomba, R., and Sanyal, A.J. (2013). The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 10, 686-690. Lu, J., Jiang, W., Yang, J.H., Chang, P.Y., Walterscheid, J.P., Chen, H.H., Marcelli, M., Tang, D., Lee, Y.T., Liao, W.S., et al. (2008). Electronegative LDL impairs vascular endothelial cell integrity in diabetes by disrupting fibroblast growth factor 2 (FGF2) autoregulation. Diabetes 57, 158-166. Mallat, Z., Heymes, C., Ohan, J., Faggin, E., Leseche, G., and Tedgui, A. (1999). Expression of interleukin-10 in advanced human atherosclerotic plaques: relation to inducible nitric oxide synthase expression and cell death. Arterioscler Thromb Vasc Biol 19, 611-616. Mehta, J.L., Chen, J., Hermonat, P.L., Romeo, F., and Novelli, G. (2006). Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders. Cardiovasc Res 69, 36-45. Mizia-Stec, K., Zahorska-Markiewicz, B., and Goliszek, L. (2003). [Adhesion molecules: atherosclerosis and coronary artery disease]. Przegl Lek 60, 147-150. Moore, K.J., Kunjathoor, V.V., Koehn, S.L., Manning, J.J., Tseng, A.A., Silver, J.M., McKee, M., and Freeman, M.W. (2005). Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. J Clin Invest 115, 2192-2201. Oeckinghaus, A., and Ghosh, S. (2009). The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 1, a000034. Olokoba, A.B., Obateru, O.A., and Olokoba, L.B. (2012). Type 2 diabetes mellitus: a review of current trends. Oman Med J 27, 269-273. Olsnes, C., Olofsson, J., and Aarstad, H.J. (2011). MAPKs ERK and p38, but not JNK phosphorylation, modulate IL-6 and TNF-alpha secretion following OK-432 in vitro stimulation of purified human monocytes. Scand J Immunol 74, 114-125. Patsch, J.R., Sailer, S., Kostner, G., Sandhofer, F., Holasek, A., and Braunsteiner, H. (1974). Separation of the main lipoprotein density classes from human plasma by rate-zonal ultracentrifugation. J Lipid Res 15, 356-366. Peng, K., Liu, L., Wei, D., Lv, Y., Wang, G., Xiong, W., Wang, X., Altaf, A., Wang, L., He, D., et al. (2015). P2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation. Int J Mol Med 35, 1179-1188. Pirillo, A., Norata, G.D., and Catapano, A.L. (2013). LOX-1, OxLDL, and atherosclerosis. Mediators Inflamm 2013, 152786. Rafieian-Kopaei, M., Setorki, M., Doudi, M., Baradaran, A., and Nasri, H. (2014). Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med 5, 927-946. Raggi, P., Genest, J., Giles, J.T., Rayner, K.J., Dwivedi, G., Beanlands, R.S., and Gupta, M. (2018). Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions. Atherosclerosis 276, 98-108. Rahaman, S.O., Lennon, D.J., Febbraio, M., Podrez, E.A., Hazen, S.L., and Silverstein, R.L. (2006). A CD36-dependent signaling cascade is necessary for macrophage foam cell formation. Cell Metab 4, 211-221. Ramkumar, S., Raghunath, A., and Raghunath, S. (2016). Statin Therapy: Review of Safety and Potential Side Effects. Acta Cardiol Sin 32, 631-639. Rhoads, J.P., Lukens, J.R., Wilhelm, A.J., Moore, J.L., Mendez-Fernandez, Y., Kanneganti, T.D., and Major, A.S. (2017). Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcgammaR Cooperation and Is Dependent on CARD9. J Immunol 198, 2105-2114. Roszer, T. (2015). Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms. Mediators Inflamm 2015, 816460. Sanchez-Quesada, J.L., Benitez, S., and Ordonez-Llanos, J. (2004). Electronegative low-density lipoprotein. Curr Opin Lipidol 15, 329-335. Schaeffer, D.F., Riazy, M., Parhar, K.S., Chen, J.H., Duronio, V., Sawamura, T., and Steinbrecher, U.P. (2009). LOX-1 augments oxLDL uptake by lysoPC-stimulated murine macrophages but is not required for oxLDL clearance from plasma. J Lipid Res 50, 1676-1684. Shan, X., Tian, L.L., Zhang, Y.M., Wang, X.Q., Yan, Q., and Liu, J.W. (2015). Ginsenoside Rg3 suppresses FUT4 expression through inhibiting NF-kappaB/p65 signaling pathway to promote melanoma cell death. Int J Oncol 47, 701-709. Shoelson, S.E., Herrero, L., and Naaz, A. (2007). Obesity, inflammation, and insulin resistance. Gastroenterology 132, 2169-2180. Slavik, J.M., Hutchcroft, J.E., and Bierer, B.E. (1999). CD80 and CD86 are not equivalent in their ability to induce the tyrosine phosphorylation of CD28. J Biol Chem 274, 3116-3124. Tang, D., Lu, J., Walterscheid, J.P., Chen, H.H., Engler, D.A., Sawamura, T., Chang, P.Y., Safi, H.J., Yang, C.Y., and Chen, C.H. (2008). Electronegative LDL circulating in smokers impairs endothelial progenitor cell differentiation by inhibiting Akt phosphorylation via LOX-1. J Lipid Res 49, 33-47. Taye, A., and El-Sheikh, A.A. (2013). Lectin-like oxidized low-density lipoprotein receptor 1 pathways. Eur J Clin Invest 43, 740-745. Tousoulis, D., Oikonomou, E., Economou, E.K., Crea, F., and Kaski, J.C. (2016). Inflammatory cytokines in atherosclerosis: current therapeutic approaches. Eur Heart J 37, 1723-1732. Walenbergh, S.M., Koek, G.H., Bieghs, V., and Shiri-Sverdlov, R. (2013). Non-alcoholic steatohepatitis: The role of oxidized low-density lipoproteins. Journal of hepatology 58, 801-810. Wang, N., Liang, H., and Zen, K. (2014). Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol 5, 614. Xu, S., Ogura, S., Chen, J., Little, P.J., Moss, J., and Liu, P. (2013). LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cell Mol Life Sci 70, 2859-2872. Yang, H., Chen, S.C., Tang, Y.Q., and Dai, Y.L. (2011). Effect of overexpression of human SR-AI on oxLDL uptake and apoptosis in 293T cells. Int Immunopharmacol 11, 1752-1757. Yang, T.C., Chang, P.Y., Kuo, T.L., and Lu, S.C. (2017a). Electronegative L5-LDL induces the production of G-CSF and GM-CSF in human macrophages through LOX-1 involving NF-kappaB and ERK2 activation. Atherosclerosis 267, 1-9. Yang, C.Y., Raya, J.L., Chen, H.H., Chen, C.H., Abe, Y., Pownall, H.J., Taylor, A.A., and Smith, C.V. (2003). Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteins. Arterioscler Thromb Vasc Biol 23, 1083-1090. Yang, T.C., Chang, P.Y., and Lu, S.C. (2017b). L5-LDL from ST-elevation myocardial infarction patients induces IL-1beta production via LOX-1 and NLRP3 inflammasome activation in macrophages. Am J Physiol Heart Circ Physiol 312, H265-H274. Yoshida, H., Kondratenko, N., Green, S., Steinberg, D., and Quehenberger, O. (1998). Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor. Biochem J 334, 9-13. Yu, X.H., Fu, Y.C., Zhang, D.W., Yin, K., and Tang, C.K. (2013). Foam cells in atherosclerosis. Clin Chim Acta 424, 245-252. Yuan, Y., Li, P., and Ye, J. (2012). Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis. Protein Cell 3, 173-181. Yuasa-Kawase, M., Masuda, D., Yamashita, T., Kawase, R., Nakaoka, H., Inagaki, M., Nakatani, K., Tsubakio-Yamamoto, K., Ohama, T., Matsuyama, A., et al. (2012). Patients with CD36 deficiency are associated with enhanced atherosclerotic cardiovascular diseases. J Atheroscler Thromb 19, 263-275. Zhang, J.M., and An, J. (2007). Cytokines, inflammation, and pain. Int Anesthesiol Clin 45, 27-37. Zhao, J.F., Ching, L.C., Huang, Y.C., Chen, C.Y., Chiang, A.N., Kou, Y.R., Shyue, S.K., and Lee, T.S. (2012). Molecular mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and atherosclerosis. Mol Nutr Food Res 56, 691-701. 周元俊 (2018) 陰電性低密度脂蛋白對巨噬細胞極化的影響: LOX-1扮演關鍵角色。國立台灣大學醫學院生物化學計分子生物學研究所碩士論文 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71068 | - |
| dc.description.abstract | 心血管疾病是全球十大致死原因之一，而動脈粥狀硬化為造成心血管疾病的主因。研究認為發炎反應在動脈粥狀硬化發展中扮演重要的角色。 LDL(-)為帶負電的低密度脂蛋白，被發現存在於動脈粥狀硬化、高膽固醇血症、第二型糖尿病及心肌梗塞等患者的血液中。先前實驗室的研究顯示從ST-時段上升型心肌梗塞(STEMI)病患所分離的LDL(-)會造成巨噬細胞產生大量的促發炎激素IL-1β。而我的研究則是探討從飲食引起的高膽固醇血症兔子所分離出的LDL(-)是否也有引起發炎反應的作用。結果顯示，STEMI病人及兔子的LDL(-)皆會誘導巨噬細胞產生大量的促發炎激素IL-1β、TNF-α、IL-6。除此之外，LDL(-)誘導NF-κB、ERK1/2、p38 及 JNK的活化。我也比較了LDL(-)與銅離子氧化的oxLDL誘導的發炎反應，結果顯示LDL(-)誘導IL-1β、TNF-α、IL-6產生及NF-κB、ERK1/2、p38 及 JNK的活化皆明顯的高於Cu-oxLDL所誘導的。 先前學長的實驗指出，LDL(-)在非酒精脂肪肝炎的發展中也扮演重要的角色。而B28號藥為實驗室的學長姐所篩選出具有預防高脂高膽固醇飼料誘發的非酒精性脂肪肝炎作用的中藥材。本實驗探討，B28號藥是否能夠抑制LDL(-)在巨噬細胞誘導的發炎反應。B28號藥為B65號藥的加工製品；首先，我比較B65與B28號藥對於LDL(-)誘導發炎的影響，結果顯示兩者皆會抑制LDL(-)誘導之發炎反應，在B28號藥的效果較為顯著。另外，B28號藥能夠抑制巨噬細胞極化成M1型。接著，我們探討B28號藥是透過何種機制抑制LDL(-)誘導巨噬細胞之作用，結果顯示，B28號藥可以有效的抑制NF-κB、ERK的活化，降低促發炎激素的產生。之前的文獻顯示，LDL(-)透過LOX-1誘導下游的訊息傳遞，並引起發炎反應。而在B28號藥處理的巨噬細胞，LOX-1的表現明顯的被抑制。因此推測B28號藥，可能是透過抑制LOX-1的表現而減少了NF-κB及ERK的活化，使得促發炎激素產生降低。最後，為分離出B28號藥之有效抗發炎的成分，我們以乙酸乙酯萃取B28號藥，並比較B28號藥粗萃物、B28號藥水層萃取物及B28號藥乙酸乙酯層萃取物對LDL(-)引起發炎反應的影響。結果顯示，B28號藥粗萃物及B28號藥乙酸乙酯層萃取物有效抑制LDL(-)誘導的發炎反應，而B28號藥水層萃取物則沒有看到此作用，因此推測B28號藥的有效抗發炎成份在乙酸乙酯萃取物中。 | zh_TW |
| dc.description.abstract | Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and atherosclerosis is the major cause of CVD. Recent research has shown that inflammation plays a crucial role in the pathogenesis of atherosclerosis. Higher levels electronegative LDL (LDL(-)) was found in plasma of patients with acute myocardial infarction, hypercholesterolemia and type II diabetes. We have recently reported that LDL(-) isolated from ST-segment elevation myocardial infarction (STEMI) induced production of IL-1β in human macrophages. Therefore, LDL(-) has inflammatory properties. In this study, we investigated whether LDL(-) isolated from hypercholesterolemic rabbits also induces inflammatory response, similar to that from STEMI patients. Our results showed that LDL(-) isolated from STEMI or hypercholesterolemic rabbits induced production of IL-1β, TNF-α and IL-6 in human macrophages. In addition, LDL(-) induced activation of NF-κB, ERK1/2, p38 and JNK. We also compared the inflammatory effects of LDL(-) with the copper-mediated oxidation of LDL (Cu-oxLDL). The results showed that LDL(-) induced higher levels of IL-1β, TNF-α and IL-6 and activation of NF-κB, ERK1/2, p38 and JNK than that induced by Cu-oxLDL. Our previous studies showed that LDL(-) also played an important role in the development of nonalcoholic steatohepatitis (NASH), and identified a chinese medicinal herb, herb-B28, which ameliorated high fat/high cholesterol (HFC) diet-induced NASH in hamster. In the second part of this study, we investigated the effects of herb-B28 on LDL(-) induced inflammation in human macrophages. Herb-B28 is the processed product of herb-B65. First, we compared the anti-inflammatory effects of herb-B28 and herb-B65 on LDL(-) induced inflammation. The results show that both herb-B28 and herb-B65 inhibited LDL(-) induced production of inflammatory cytokines in human macrophages; In addition, the anti-inflammatory effect of herb-B28 is more potent than herb-B65. Moreover, herb-B28 inhibited LDL(-) induced polarization of macrophage into M1 phenotype. We also showed that herb-B28 suppressed the production of inflammatory cytokines through reducing LOX-1 expression and inhibiting the activation of NF-κB and ERK1/2. In order to search for the effective anti-inflammatory component of herb-B28, herb-B28 was extracted with ethyl acetate. The effects of ethyl acetate extracted B28 (EA28) and water soluble fraction of B28 (W28) on LDL(-) induced production of inflammatory cytokines were investigated. The results showed that the anti-inflammatory effects of EA28 was similar to that of herb-B28, but W28 had no effect. Therefore, the effective anti-inflammatory compounds of herb-B28 is mainly in the ethyl acetate fraction. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T04:51:20Z (GMT). No. of bitstreams: 1 ntu-107-R05442026-1.pdf: 7488993 bytes, checksum: 118fe8c8d32527185156c147a9cb7ae3 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 口試委員審定書 i 誌謝 ii 摘要 iii Abstract v 第一章 、緒論 1 第一節、文獻回顧 2 第二節、研究動機以及實驗目的 10 第二章 、材料方法 12 第一節、實驗材料 13 第二節、動物實驗 15 第三節、銅離子誘導低密度脂蛋白氧化 (Cu-oxLDL) 17 第四節、細胞實驗 17 第五節、酵素結合免疫吸附法(Enzyme-Linked ImmunoSorbent Assay, ELISA)……………………………………………………………………………18 第六節、油紅染色 (Oil red O staining) 19 第七節、中草藥配製與分配萃取 19 第八節、MTT 試驗 20 第九節、細胞mRNA表現分析 20 第十節、西方點墨法 (Western blotting) 23 第十一節、統計分析 25 第三章 、實驗結果 27 第一節、 LDL(-)誘導巨噬細胞產生 IL-1β、TNF-α以及IL-6 28 第二節、 LDL(-)以及oxLDL皆會促成泡沫細胞的形成 28 第三節、 比較不同氧化程度之LDL誘導巨噬細胞產生促發炎因子 29 第四節、 LDL(-)及oxLDL對於巨噬細胞中NF-κB的影響 29 第五節、 LDL(-)及oxLDL對於巨噬細胞中MAPKs的影響 30 第六節、 LDL(-)誘導巨噬細胞產生IL-1β、TNF-α、IL-6的可能機制 30 第七節、 比較LDL(-)以及LDL(-)-oxLDL誘導巨噬細胞產生促發炎因子 30 第八節、 B28號藥及B65號藥萃取 31 第九節、 B28號藥、B65號藥以及LDL(-)對於細胞存活率之影響 31 第十節、 B28號藥明顯抑制LDL(-)誘導巨噬細胞產生IL-1β、TNF-α、IL-6 32 第十一節、 B28號藥對巨噬細胞極化的影響 32 第十二節、 B28號藥抑制LDL(-)誘導巨噬細胞NF-κB活化 33 第十三節、 B28號藥抑制LDL(-)誘導巨噬細胞ERK路徑活化 33 第十四節、 B28號藥減少巨噬細胞Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) 受體的表現 34 第十五節、 B28號藥的萃取分層 34 第十六節、 W28、EA28以及LDL(-)對於巨噬細胞存活率的影響 34 第十七節、 B28號藥分層萃取物對LDL(-)誘導巨噬細胞分泌IL-1β、TNF-α以及IL-6的影響 35 第四章、討論 36 第一節、 高膽固醇血症兔子與STEMI病患血液分離出的LDL(-)作用類似 37 第二節、 LDL(-)與oxLDL皆會促使巨噬細胞形成泡沫細胞 (foam cell) 37 第三節、 LDL(-)誘導巨噬細胞產生促發炎因子較oxLDL更加顯著 38 第四節、 LDL(-)透過活化NF-κB以及MAPKs引起發炎反應 39 第五節、 B28號藥具有抑制LDL(-)引起發炎反應 40 第六節、 B28號藥抑制巨噬細胞極化成M1型 41 第七節、 B28號藥減緩LDL(-)誘導發炎反應之機制 42 第八節、 B28號藥抗發炎有效成分於乙酸乙酯層 43 第九節、 總結 43 第五章 、圖表 45 參考文獻 72 | |
| dc.language.iso | zh-TW | |
| dc.subject | 抗發炎 | zh_TW |
| dc.subject | 動脈粥狀硬化 | zh_TW |
| dc.subject | 高膽固醇血症 | zh_TW |
| dc.subject | 陰電性低密度脂蛋白 | zh_TW |
| dc.subject | 氧化低密度脂蛋白 | zh_TW |
| dc.subject | 泡沫細胞 | zh_TW |
| dc.subject | 發炎反應 | zh_TW |
| dc.subject | Inflammation | en |
| dc.subject | Atherosclerosis | en |
| dc.subject | Anti-inflammation | en |
| dc.subject | oxLDL | en |
| dc.subject | Hypercholesterolemia | en |
| dc.subject | LDL(-) | en |
| dc.subject | Foam cell | en |
| dc.title | 陰電性低密度脂蛋白引起巨噬細胞發炎反應之探討 | zh_TW |
| dc.title | Study on electronegative LDL-induced inflammation in human macrophages | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳惠玲,張淑芬,張博淵,何承懋 | |
| dc.subject.keyword | 動脈粥狀硬化,高膽固醇血症,陰電性低密度脂蛋白,氧化低密度脂蛋白,泡沫細胞,發炎反應,抗發炎, | zh_TW |
| dc.subject.keyword | Atherosclerosis,Hypercholesterolemia,LDL(-),oxLDL,Foam cell,Inflammation,Anti-inflammation, | en |
| dc.relation.page | 83 | |
| dc.identifier.doi | 10.6342/NTU201802245 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-107-1.pdf 未授權公開取用 | 7.31 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。