( 您好!臺灣時間:2021/05/06 12:49
字體大小: 字級放大   字級縮小   預設字形  


論文名稱:台灣佳葉龍茶(GABA tea)萃取液抗先天性高血壓大白鼠(SHR)心肌凋亡分子機轉探討
論文名稱(外文):Molecular Mechanisms of Antiapoptotic Effects of GABA Tea on Spontaneously Hypertensive Rat (SHR) Hearts
指導教授(外文):Kan-Jen Tsai
  • 被引用被引用:2
  • 點閱點閱:188
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
心肌細胞凋亡是造成心臟衰竭的主因。實驗的目的在探討台灣佳葉龍茶(GABA tea)萃取液抗先天性高血壓大白鼠(SHR)心肌凋亡之分子機轉。我們採用雄性八週齡先天性高血壓大白鼠,約200公克,經適應五週後分成六組,每組5-6隻動物。並將此六組先天性高血壓大白鼠分別餵食水(water/20ml/day/rat)、高劑量(301μgGABA/extracting tea/20ml/day/rat) 佳葉龍茶(HGT)、低劑量(151μgGABA/extracting tea/20ml/day/rat)佳葉龍茶湯(LGT)、高(301μgGABA/20ml/day/rat) 純GABA溶液(HG)與低(151μgGABA/20ml/day/rat)純GABA溶液(LG)及綠茶湯(20ml/day/rat)(GT)。所有動物,均採自由攝食飼料與實驗樣品12週,再進一步探討與心肌細胞凋亡及存活等相關路徑。我們首先從H&E 染色的心臟切片中發現GABA和green tea有減緩SHR心肌細胞傷害的情形。並在TUNEL assay中觀察到GABA和green tea具可抑制SHR產生的心肌細胞凋亡的情形。進一步採用Western Blot分析,發現SHR心肌細胞凋亡,同時透過Death receptor dependent及Mitochondria dependent這兩條路徑。而GABA和green tea不僅具抑制此兩條凋亡路徑之作用,同時活化了IGF-I及PI3K/Akt心肌存活路徑來保護SHR的心肌細胞且以上的作用均以LG及GT為佳。由以上的研究結果,使我們相信適量的GABA及green tea均具有保護心肌細胞的作用。相信適量的GABA及green tea給予,應可降低高血壓治療用藥的劑量和依賴程度。

Background:Cardiomyocytes apoptosis is the major risk factor for the development of heart failure (HF). The purpose of this study was to evaluate the effects of GABA tea on hypertension induced cardiac apoptotic pathways in SHR. Methods: In order to reveal the mechanisms, thirty-six male spontaneously hypertensive rats (SHR) at eight weeks of age, 200g were divided into six groups .One group was fed water as a background control group.other rats were administered one of the following treatments: GABA tea at dose 150 and 300 mg/kg BW as LGT and HGT groups,respectively, pure GABA at dose 150 and 300 mg/kg BW as LG and HG groups,respectively , green tea(GT) as control of LGT and HGT groups. After 12 weeks,cardiac tissues were analyzed by histological analysis, western blotting and TUNEL assays. Results: GABA tea, green tea and pure GABA ,decreased hypertension -induced cardiac abnormalities,including abnormal myocardial architecture, enlarged interstitial spaces, and more cardiac TUNEL-positive apoptotic cells. In addition,GABA tea ,green tea and pure GABA, decreased protein levels of Fas ligand, Fas death receptors,FADD,Bax and Bak, and dramatically increased anti-apoptotic proteins ,Bcl2.Further more GABA tea green tea and pure GABA also decreased activated-Caspase8,activated-caspase 9 and activated-caspase 3. Additionally, the expressions of IGF-I and PI3K/Akt pathway, maintaining the survival to cardiomyocytes were also upregulated.All of the above result , LG and green tea anti-apoptotic and pro-survival effects showed the best. Conclusion: The cardioprotective effect of GABA tea green tea and pure GABA can be attributed to not only antioxidant and antihypertensive properties but also improvement of the cardiomyctye apoptosis by induced hypertension .

中文摘要 1
Abstract 2
壹、緒論 3
貳、背景介紹 10
参、研究動機 28
肆、實驗方法 29
伍、實驗材料 35
陸、結果 40
柒、討論 48
捌、參考文獻 54
圖表 62

1.Yusuf S, Reddy S, Ôunpuu S, Anand S. Global Burden of Cardiovascular Diseases: Part I: General Considerations, the Epidemiologic Transition, Risk Factors, and Impact of Urbanization. Circulation 2001;104:2746-53.
2. Balch, Phyllis A., Prescription for Nutritional Healing, 3rd Ed, New York,
2000,Balch, Phyllis A., Prescription for Herbal Healing, 1st Ed, New York, Avery, 2002.
3. Parati G, Pomidossi G, Albini F, et al. Relationship of 24-hour blood pressure mean and variability to severity of target organ damage in hypertension. J Hypertens 1987; 5:93–98.
4. Frattola A, Parati G, Cuspidi C, et al. Prognostic value of 24-hour blood
pressure variability. J Hypertens 1993; 11:1133–1137.
5. Su DF, Miao CY. Reduction of blood pressure variability: a new strategy
for the treatment of hypertension. Trends Pharmacol Sci 2005; 26:388–390.
6. Lippincott Williams & Wilkins 0268-4705 Current Opinion in Cardiology 2006, 21:486–491.
7. Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev 1999; 79:215–262.
8. European Journal of Clinical Nutrition (2003) 57, 490–495.
9. Takahashi H, Tiba M, Iino M & Takayasu T (1955): The effect of g-amino
butyri acid on blood pressure. Jpn. J. Physiol. 5, 334 – 341.
10. Elliott KAC & Hobbiger F (1959): Gamma aminobutyric acid: circulatory
and respiratory effects in different species: re-investigation of the anti-strychnine
action in mice. J. Physiol. 146, 70– 84.
11. Ueno,H.(2000)Enzymatic and structural aspects on glutamate decarbo-
xylase. J.Molecular Catalysis B: Enzymatic.10:67-79.
12. Stanton HC (1963): Mode of action of gamma aminobutyric acid on the cardiovascular system. Arch. Int. Pharmacodyn. 143, 195 – 204.
13. Takahashi, H., Tiba,M.and Iino,M.(1955) effect of GABA on blood pressure,Jpn.J.Physiol.5:334-341.
14. Fagg,C.E.and Foster,A.C.(1983) Amino acid neurotransmitters and their pathway in the mammalian central nervous system. Neurosciencs 9:701-719.
15. Laakmann,G.,Treusch,J.,Eichmeier,A.,Schmauss,M., Treusch,U.(1982)
Inhibitory effect of phenotolamine on diazepam-induced growth hormone secretion and lack of effect of diazepam on prolactin secretion in man.Psychoneuroendocrinology7:135-139.
16. Vescovi, P. P., Volpi, R. and Coiro, V.(1998) Alcoholism abolishes the Gamma aminobutyric acid(GABA)ergic control of GH secretion in humans. Alcohol 16(4):325-328.
17. Kihara, M. and Kubo, T.(1989) Immunocytochemical localization of GABA containing neurons in the ventrolateral medulla oblongata of the rat.Histochemistry.91:301-314.
18. Hayakawa K, Kimura M & Kamata K (2002): Mechanism underlying
gamma-aminobutyric acid-induced antihypertensive effect in spontaneously
hypertensive rats. Eur. J. Pharmac. 438, 107 – 113.
19. Gomez, R. and Barros, H. M. T. (2000)Ethopharmacology of the
antidepressant effect of clonazepam in diabetic rats.Pharmacology Biochemistry and Behavior 66(2):329-335.
20. Murck, H., Antonijevic, I. A., Schier, T., Frieboes, R. M., Barthelmes, J. and Steiger, A.(1999) Aging does not affect the sleep endocrine response to total sleep deprivation in humams. Neurobiology of Aging 20:665-668.
21. Wegwliu, K.,Halonen, T. and Korpi, E. R. (1993) Gamma-viny GABA decreases voluntary alcohol consumption in alcohol-preferring rats. Pharmacol. Toxicol.73:150-152.
22. Mergl, Z., Acs, Z. and Makara, G. B.(1995) Growth hormone secretion and activation of cyclic AMP by growth hormone releasing hormone and gamma- aminobutyric acid in the neonatal rat pituitary. Life Science 56(8):579-585.
23. Shiah,I. S., Robertson, H. A., Lam, R. W., Yatham, L. N., Tam, E. M. and Zis, A. P.(1999) Psychoneuroendocrinology24:195-204.
24. Kano, T., Shimizu-Sasamata, M., Huang, P. L., Moskowitz, M. A. and Lo, E. H.(1998) Effects of nitic oxide synthase gene knockout on neurotransmitter release in vivo. neuroscience 86(3):695-699.
25. Kirik, D., Rosenblad, C., bjorklund, A. and Mandel, R. J. (2000) Long-term rAAV-mediated gene transfer of GDNF in the rat Parkinson’s model :Intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system. J. neurosci. 20:4686-4700.
26. Lundberg, C. S., Jungles, S. J. and Mulligan, R. C. (2001) Direct delivery of leptin to the hypothalamus using recombinant adeno-associated virus vectors results in increased therapeutic efficacy. Nat.Biotechnol. 19:169-172.
27. Moss, H. B., Yao, J. K., Buens, M., Maddock, J. and Tarter, R. E.(1990) Plasma GABA-like activity in response to ethanol chanllenge in men at high risk for alcoholism. Bio. Psychiatry. 27:617-625.
28. Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 27, 2006; DOI: 10.1124/jpet.106.109538.
29. Zhang K, Li YF, and Patel KP (2002) Reduced endogenous GABA-mediated inhibition in the PVN on renal nerve discharge in rats with heart failure. Am J Physiol 282: R1006–R1015.
30. Zhang K and Patel KP (1998) Effect of nitric oxide within the paraventricular nucleus on renal sympathetic nerve discharge: role of GABA. Am J Physiol 275: R728–R734.
31. Takenaka K, Sasaki S, Uchida A, Fujita H, Nakamura K, Ichida T, Itoh H, Nakata T, Takeda K, Nakagawa M. 1: Am J Hypertens. 1996 Oct;9(10 Pt 1):964-72.
32. DeFeudis FV. Experientia. 1983 Aug 15;39(8):845-9.
33. Roberts E, Krause DN Isr J Med Sci. 1982 Jan;18(1):75-81.
34. Paco Lorente , Alain Lacampagne, Yvan Pouzeratte, Stephen Richards,
Barbara Malitschek, Rainer Kuhn, Bernhard Bettler, and Guy Vassort PNAS | July 18, 2000 | vol. 97 | no. 15 | 8664-8669.
35. Ueno, H. (2000) Enzymatic and structural aspects on glutamate carboxylase. J. Molecular Catalysis B: Enzymatic. 10:67-79.
36. Omori, M., Yano, T., Okamoto J. Tsushida, T., Murai, T. and Higuchi, M.(1987) Effect of anaerobically treated tea (Gabaron tea) on blood pressure of spontaneously hypertensive rat. Nippon Nogeikagaku Kaishi 61(11):1449-1451.
37. Tsushida, T., Murai, T., Omori, M. and Okamoto, J. (1987) Production of a new type tea containing a high level of gamma aminobutyric acid. Nippon Nogeikagaku kaishi 6(7): 817-822.
38. Bushman, J. L. (1998) Green tea and cancer in human : a review of the literature . Nutr. cancer 33:125-131.
39. Marian AJ, Roberts R. Recent advances in the molecular genetics of hypertrophic cardiomyopathy. Circulation 1995;92(5):1336-47.
40. van Bilsen M, Chien KR. Growth and hypertrophy of the heart: towards an understanding of cardiac specific and inducible gene expression. Cardiovascular research 1993;27(7):1140-9.
41. Sugden PH, Clerk A. Cellular mechanisms of cardiac hypertrophy. Journal of molecular medicine (Berlin, Germany) 1998;76(11):725-46.
42. Chien KR. Stress pathways and heart failure. Cell 1999;98(5):555-8.
43. Nicol RL, Frey N, Olson EN. From the sarcomere to the nucleus: role of genetics and signaling in structural heart disease. Annual review of genomics and human genetics 2000;1:179-223.
44. Vassiliadis N, Vassiliadis K, Karkavelas G. Sudden death due to cardiac myxoma. Medicine, science, and the law 1997;37(1):76-8.
45. Anversa P, Ricci R, Olivetti G. Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: a review. Journal of the American College of Cardiology 1986;7(5):1140-9.
46. Gardner DG. Natriuretic peptides: markers or modulators of cardiac hypertrophy? Trends in endocrinology and metabolism: TEM 2003;14(9):411-6.
47. Chien KR, Zhu H, Knowlton KU, et al. Transcriptional regulation during cardiac growth and development. Annual review of physiology 1993;55:77-95.
48. Akazawa H, Komuro I. Roles of cardiac transcription factors in cardiac hypertrophy. Circulation research 2003;92(10):1079-88.
49. Sadoshima J, Izumo S. The cellular and molecular response of cardiac myocytes to mechanical stress. Annual review of physiology 1997;59:551-71.
50. Mukoyama M, Nakao K, Hosoda K, et al. Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. The Journal of clinical investigation 1991;87(4):1402-12.
51. Hansson GK. Cell-mediated immunity in atherosclerosis. Current opinion in lipidology 1997;8(5):301-11.
52. Lee RT, Libby P. The unstable atheroma. Arteriosclerosis, thrombosis, and vascular biology 1997;17(10):1859-67.
53. Poli V. The role of C/EBP isoforms in the control of inflammatory and native immunity functions. The Journal of biological chemistry 1998;273(45):29279-82.
54. Sturgill TW, Wu J. Recent progress in characterization of protein kinase cascades for phosphorylation of ribosomal protein S6. Biochimica et biophysica acta 1991;1092(3):350-7.
55. Dalby KN, Morrice N, Caudwell FB, Avruch J, Cohen P. Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK. The Journal of biological chemistry 1998;273(3):1496-505.
56. Clerk A, Sugden PH. Activation of protein kinase cascades in the heart by hypertrophic G protein-coupled receptor agonists. The American journal of cardiology 1999;83(12A):64H-9H.
57. Force T, Pombo CM, Avruch JA, Bonventre JV, Kyriakis JM. Stress-activated protein kinases in cardiovascular disease. Circulation research 1996;78(6):947-53.
58. Sugden PH, Clerk A. "Stress-responsive" mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circulation research 1998;83(4):345-52.
59. Abe J, Baines CP, Berk BC. Role of mitogen-activated protein kinases in ischemia and reperfusion injury : the good and the bad. Circulation research 2000;86(6):607-9.
60. Ruwhof C, van der Laarse A. Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovascular research 2000;47(1):23-37.
61. Bueno OF, De Windt LJ, Lim HW, et al. The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo. Circulation research 2001;88(1):88-96.
62. Lee JD, Ulevitch RJ, Han J. Primary structure of BMK1: a new mammalian map kinase. Biochemical and biophysical research communications 1995;213(2):715-24.
63. Zhou G, Bao ZQ, Dixon JE. Components of a new human protein kinase signal transduction pathway. The Journal of biological chemistry 1995;270(21):12665-9.
64. English JM, Vanderbilt CA, Xu S, Marcus S, Cobb MH. Isolation of MEK5 and differential expression of alternatively spliced forms. The Journal of biological chemistry 1995;270(48):28897-902.
65. Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD. BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. The EMBO journal 1997;16(23):7054-66.
66. Fukuhara S, Marinissen MJ, Chiariello M, Gutkind JS. Signaling from G protein-coupled receptors to ERK5/Big MAPK 1 involves Galpha q and Galpha 12/13 families of heterotrimeric G proteins. Evidence for the existence of a novel Ras AND Rho-independent pathway. The Journal of biological chemistry 2000;275(28):21730-6.
67. Takeishi Y, Abe J, Lee JD, Kawakatsu H, Walsh RA, Berk BC. Differential regulation of p90 ribosomal S6 kinase and big mitogen-activated protein kinase 1 by ischemia/reperfusion and oxidative stress in perfused guinea pig hearts. Circulation research 1999;85(12):1164-72.
68. Kamakura S, Moriguchi T, Nishida E. Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. Identification and characterization of a signaling pathway to the nucleus. The Journal of biological chemistry 1999;274(37):26563-71.
69. Nicol RL, Frey N, Pearson G, Cobb M, Richardson J, Olson EN. Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. The EMBO journal 2001;20(11):2757-67.
70. Wang Y, Huang S, Sah VP, et al. Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. The Journal of biological chemistry 1998;273(4):2161-8.
71. Zhu W, Zou Y, Aikawa R, et al. MAPK superfamily plays an important role in daunomycin-induced apoptosis of cardiac myocytes. Circulation 1999;100(20):2100-7.
72. Kang YJ, Zhou ZX, Wang GW, Buridi A, Klein JB. Suppression by metallothionein of doxorubicin-induced cardiomyocyte apoptosis through inhibition of p38 mitogen-activated protein kinases. The Journal of biological chemistry 2000;275(18):13690-8.
73. Communal C, Colucci WS, Singh K. p38 mitogen-activated protein kinase pathway protects adult rat ventricular myocytes against beta -adrenergic receptor-stimulated apoptosis. Evidence for Gi-dependent activation. The Journal of biological chemistry 2000;275(25):19395-400.
74. Craig R, Larkin A, Mingo AM, et al. p38 MAPK and NF-kappa B collaborate to induce interleukin-6 gene expression and release. Evidence for a cytoprotective autocrine signaling pathway in a cardiac myocyte model system. The Journal of biological chemistry 2000;275(31):23814-24.
75. Hoover HE, Thuerauf DJ, Martindale JJ, Glembotski CC. alpha B-crystallin gene induction and phosphorylation by MKK6-activated p38. A potential role for alpha B-crystallin as a target of the p38 branch of the cardiac stress response. The Journal of biological chemistry 2000;275(31):23825-33.
76. Hunter JJ, Chien KR. Signaling pathways for cardiac hypertrophy and failure. The New England journal of medicine 1999;341(17):1276-83.
77. Jacobson MD, Weil M, Raff MC. Programmed cell death in animal development. Cell 1997;88(3):347-54.
78. Yamamoto S, Sawada K, Shimomura H, Kawamura K, James TN. On the nature of cell death during remodeling of hypertrophied human myocardium. Journal of molecular and cellular cardiology 2000;32(1):161-75.
79. Narula J, Haider N, Virmani R, et al. Apoptosis in myocytes in end-stage heart failure. The New England journal of medicine 1996;335(16):1182-9.
80. Olivetti G, Abbi R, Quaini F, et al. Apoptosis in the failing human heart. The New England journal of medicine 1997;336(16):1131-41.
81. Willingham MC. Cytochemical methods for the detection of apoptosis. J Histochem Cytochem 1999;47(9):1101-10.
82. Haunstetter A, Izumo S. Apoptosis: basic mechanisms and implications for cardiovascular disease. Circulation research 1998;82(11):1111-29.
83. Li P, Nijhawan D, Budihardjo I, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997;91(4):479-89.
84. Reed JC. Double identity for proteins of the Bcl-2 family. Nature 1997;387(6635):773-6.
85. Rosse T, Olivier R, Monney L, et al. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 1998;391(6666):496-9.
86. Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science (New York, NY 1998;281(5381):1322-6.
87. Reed JC. Bcl-2 family proteins. Oncogene 1998;17(25):3225-36.
88. Kelekar A, Thompson CB. Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends in cell biology 1998;8(8):324-30.
89. Sattler M, Liang H, Nettesheim D, et al. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science (New York, NY 1997;275(5302):983-6.
90. Schendel SL, Azimov R, Pawlowski K, Godzik A, Kagan BL, Reed JC. Ion channel activity of the BH3 only Bcl-2 family member, BID. The Journal of biological chemistry 1999;274(31):21932-6.
91. Li H, Zhu H, Xu CJ, Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 1998;94(4):491-501.
92. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 1998;94(4):481-90.
93. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 1997;90(3):405-13.
94. Lee HY, Chun KH, Liu B, et al. Insulin-like growth factor binding protein-3 inhibits the growth of non-small cell lung cancer. Cancer research 2002;62(12):3530-7.
95. LeRoith D, Werner H, Beitner-Johnson D, Roberts CT, Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocrine reviews 1995;16(2):143-63.
96. Werner H, Le Roith D. The insulin-like growth factor-I receptor signaling pathways are important for tumorigenesis and inhibition of apoptosis. Critical reviews in oncogenesis 1997;8(1):71-92.
97. Nissley P, Lopaczynski W. Insulin-like growth factor receptors. Growth factors (Chur, Switzerland) 1991;5(1):29-43.
98. Lund PK, Moats-Staats BM, Hynes MA, et al. Somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues. The Journal of biological chemistry 1986;261(31):14539-44.
99. Murphy LJ, Bell GI, Friesen HG. Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat. Endocrinology 1987;120(4):1279-82.
100. Rotwein P, Pollock KM, Watson M, Milbrandt JD. Insulin-like growth factor gene expression during rat embryonic development. Endocrinology 1987;121(6):2141-4.
101. Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A, Pols HA. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. The Journal of clinical endocrinology and metabolism 2002;87(8):3632-9.
102. Li Q, Li B, Wang X, et al. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. The Journal of clinical investigation 1997;100(8):1991-9.
103. Cheng TO.All teas are not created equal: the Chinese green tea and cardiovascular health.Int J Cardiol. 2006 Apr 14;108(3):301-8. Epub 2005 Jun 22. Review.
104. Vinson JA.Black and green tea and heart disease: a review.Biofactors. 2000;13(1-4):127-32. Review.
105. Weisburger JH.Tea and health: the underlying mechanisms.Proc Soc Exp Biol Med. 1999 Apr;220(4):271-5. Review.

第一頁 上一頁 下一頁 最後一頁 top
1. 17.黃雅儀、謝秀敏、陳素根、張菀真(2009),「病人安全風氣知覺之相關因素探討-以中部某教學醫院護理人員為例」,《長庚護理》,第20卷第1期,26-36。
2. 17.黃雅儀、謝秀敏、陳素根、張菀真(2009),「病人安全風氣知覺之相關因素探討-以中部某教學醫院護理人員為例」,《長庚護理》,第20卷第1期,26-36。
3. 1.石崇良(2008),「醫療團隊合作與病人安全」,《澄清醫護管理雜誌》,第4卷第1期,5-9。
4. 26.羅健銘、張斐綾、廖熏香、李偉強(2008),「病人安全文化分析」,《醫療品質雜誌》,第2卷第4期,68-73。
5. 26.羅健銘、張斐綾、廖熏香、李偉強(2008),「病人安全文化分析」,《醫療品質雜誌》,第2卷第4期,68-73。
6. 25.顏如娟、許明暉(2008),「論病人安全文化對醫療體系的衝擊」,《北市醫學雜誌》,第5卷第2期,1-12。
7. 1.石崇良(2008),「醫療團隊合作與病人安全」,《澄清醫護管理雜誌》,第4卷第1期,5-9。
8. 14.陳綺芬、林雅真、江素真、周珊珊、吳孟凌(2008),「提升住院病人辨識率」,《北市醫學雜誌》,第5卷第1期,163-171。
9. 25.顏如娟、許明暉(2008),「論病人安全文化對醫療體系的衝擊」,《北市醫學雜誌》,第5卷第2期,1-12。
10. 14.陳綺芬、林雅真、江素真、周珊珊、吳孟凌(2008),「提升住院病人辨識率」,《北市醫學雜誌》,第5卷第1期,163-171。
11. 13.陳玉枝、簡淑芬、李偉強(2008),「某醫學中心對護理人員職埸安全態度之調查」,《榮總護理》,第25卷第2期,179-187。
12. 13.陳玉枝、簡淑芬、李偉強(2008),「某醫學中心對護理人員職埸安全態度之調查」,《榮總護理》,第25卷第2期,179-187。
13. 12.徐永年、徐錦池(2010),「醫護人員求援機制:團隊合作降低醫療糾紛」,《醫療品質雜誌》,第4卷第2期,12-15。
14. 12.徐永年、徐錦池(2010),「醫護人員求援機制:團隊合作降低醫療糾紛」,《醫療品質雜誌》,第4卷第2期,12-15。
15. 10.吳麗蘭(2008),「醫院員工對病人安全之認知與態度調查」,《北市醫學雜誌》,第5卷第1期,75-85。
系統版面圖檔 系統版面圖檔