(18.206.238.77) 您好!臺灣時間:2021/05/17 17:10
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:張木信
研究生(外文):Mu-Hsin
論文名稱:探討心室中膈缺損幼童及接受冠狀動脈手術患者之心肌類胰島素生長因子及接受體訊息路徑的表現差異
論文名稱(外文):Investigate the expression of IGF-I and IGF-IRsignaling pathways in ventricular septal defect infantsand coronary artery bypass surgery patients
指導教授:吳文俊吳文俊引用關係楊肇基楊肇基引用關係
學位類別:博士
校院名稱:中山醫學大學
系所名稱:醫學分子毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:75
相關次數:
  • 被引用被引用:0
  • 點閱點閱:145
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
Part-I
高鉀離子心臟麻醉灌流液(high KCl cardioplegia solution)是在心臟外科手術最常使用的方法。然而,高鉀離子心臟麻醉灌流液對心臟組織的副作用影響尚待釐清。目前的研究進一步探討鉀離子心臟麻醉灌流液是否誘發心肌細胞凋亡與心臟纖維化及其相關機轉。在冠狀動脈心臟病人進行高鉀離子心臟麻醉/冠動脈支路嫁接(CABG)治療之手術期間前後,游離小部分右心房組織(病人n = 20)。同時,使用鉀離子心臟麻醉灌流液及15 mM KCl solution處理H9c2心肌細胞、初代培養心肌細胞和初代培養纖維母細胞探討高鉀離子誘發心肌細胞凋亡與心臟纖維化的機轉。由TUNEL assay觀察到在CABG治療手術後的心臟組織檢體以及在高鉀離子溶液處裡過的心肌細胞都有明顯心肌細胞凋亡的現象。從Western Blot assay結果發現高鉀離子的確會誘發促凋亡蛋白(Bad, released cytochrome c and active caspase-3)大量表現。除此之外,高鉀離子更誘發non-cardiomyocyte ptoliferation-related IGF-I/IGF-IR/ERK pathway活化及cardiac fibrosis-related factors (uPA,
MMP-2, MMP-9, Sp-1 and CTGF)大量表現。然而心肌細胞survival
factor (Akt)表現量卻明顯地被高鉀離子抑制。綜合以上結果得知:高鉀離子透過誘發mitochondrial injury和Akt減少進而引起心肌細胞凋亡。同時伴隨著促非心肌細胞增生相關訊息途徑(IGF-I/IGF-IR/ERK pathway)活化與纖維化相關因子(MMP-2, MMP-9, Sp-1 and CTGF)的大量表現更加促使心臟功能衰竭的進行。此機轉解釋了心肌細胞凋亡如何在CABG治療之手術期間被誘發,並且暗示CABG治療手術之延長可能進一步引起心臟纖維化的癒後不全。

Part-II
先前我們的研究已發現,心室中隔缺損新生兒血清中的IGF-1濃度有
顯著性的下降,並且生長荷爾蒙會隨之增加。然而,為了確定IGF-1
及心室中隔缺損兩者之間的關係,我們進一步探討IGF-1及IGF-IR基
因在心室中隔缺損新生兒心肌組織的表現情形。首先,收集27位新生兒右心房組織進行研究。將組織進行分類: 5位沒有心室中隔缺損之新生兒分類為控制組(Group 1);20位心室中隔缺損新生兒依據分流大小指數QP/QS(Shunting magnitude index)分成二組:中度分流(QP/QS <1.7)病患為實驗組二(Group II),重度分流(Qp/Qs ≥ 2)患者為實驗組三(Group III);此外,重度法洛氐四重症(TOF)以及分流指數Qp/Qs >4 新生兒則分類為實驗組四(Group Ⅳ)。利用非放射線DIG-RNA探針、西方墨點轉漬法及免疫組織化學染色等系統來測定心室中隔缺損新生兒右心房類胰島素生長因子及接受體基因表現。實驗結果顯示,在四個組別中,IGF-1以及IGF-IR蛋白質表現量分別為0.95 ± 0.05,100.42 ± 0.03, 0.29± 0.07, 0.23 ± 0.05以及0.79± 0.09, 0.58 ± 0.02, 0.37±0.02, 0.28 ± 0.04。另外IGF-1以及IGF-IR mRNA表現量為0.95 ± 0.01,0.41 ± 0.03, 0.29 ± 0.05, 0.15 ± 0.01及0.85 ± 0.05, 0.56 ± 0.03, 0.17 ±
0.01, 0.18 ± 0.01。與控制組(Group I)相比,Group II(p<0.05)、GroupIII、Group Ⅳ(p<0.01) IGF-1以及IGF-IR蛋白質及mRNA 表現量皆有顯著且逐漸減少的情形。在免疫組織化學染色結果也顯示相同的降低表現情形。此外,在心室中隔缺損的新生兒中,IGF-1、IGF-IR蛋白質及mRNA表現下降也與右心房飽和氧以及心臟收縮RVP/LVP比率有關。由以上實驗結果顯示,我們證實心室中隔缺損的新生兒心肌組織中IGF-1、IGF-IR表現量會下降,並且此現象與分流大小指數以及心臟腔室嚴重血氧缺乏有其關係性。

Part-I
Infusion of high KCl cardioplegia solution is the most common method for inducing asystole before cardiac surgery. However, the effects of cardioplegic solution on cardiac tissues and cells remain unclear. The present study examined the mechanisms behind cardiomyocyte apoptosis and cardiac fibrosis in patients who are administered high KCl cardioplegic solution prior to undergoing coronary artery bypass graft (CABG) to treat coronary artery disease (CAD). Two sequential biopsy
specimens were obtained from the right atriums during the
precardioplegic and postcardioplegic arrest periods in 20 CAD patients undergoing CABG surgery. In addition, cardiomyoblast H9c2 cells, primary neonatal cardiomyocytes and cardiac fibroblasts were treated with high KCl cardioplegic solution and 15 mM KCl solution to detect
the mechanisms behind cardiomyocyte apoptosis and cardiac fibrosis. TUNEL assay revealed increased levels of myocardiac cell apoptosis in biopsy specimens of the right atriums of patients who had been administered high KCl cardioplegic solution during CABG, and in H9c2 cells that had been exposed to high KCl cardioplegic solution and 15 mM KCl solution. Western blot showed increased activation of proapoptotic Bad, greater levels of released cytochrome c and active caspase-3 in postcardioplegic right atriums and in H9c2 cells exposed to high KCl cardioplegic solution and 15 mM KCl solution. The IGF-I/IGF-IR/ERK
pathway, known to be involved in cardiac fibroblast proliferation, and the expression/activation of uPA, MMP-2, MMP-9, Sp-1 and CTGF, which are known to be involved in the development of cardiac fibrosis, were up-regulated in postcardioplegic right atriums and cardiac fibroblasts.
However, the activation of survival factor Akt was greatly decreased in postcardioplegic right atriums and in cultured cardiomyocytes. These data suggest that high KCl cardioplegia appears to induce mitochondrial injury
and inactivation of Akt, resulting in apoptosis of cardiomyocytes. The activated IGF-I/IGF-IR/ERK pathway and the upregulation of uPA, MMP-2, MMP-9, Sp-1 and CTGF in cardiofibroblast cells further promote the development of cardiac fibrosis. The mechanism explains how cardiomyocyte apoptosis is induced during CABG surgery in CAD
patients, and might imply that the risk of cardiac fibrosis is dependent on the duration of surgery.

Part-II
Our previous studies showed serum insulin-like growth factor-I (IGF-I) concentrations significantly decreased in infants with congenital ventricular septal defect (VSD) and that they were associated with increased concentrations of growth hormone. In order to confirm the
relationship between IGF-I axis and VSD, we further compared the IGF-I and insulin-like growth factor-I receptor (IGF-IR) gene expressions in the cardiac tissue of VSD infants. Right atrium biopsies of 27 infants were
studied. Five infants not having VSD were classified as controls (Group I). Twenty VSD patients were then divided into 2 groups according to their shunting magnitude index (level of pulmonary vascular resistance compared with systemic vascular resistance, Qp/Qs). VSD patients with
minor shunts (Qp/Qs&lt;1.7) were classified as Group II; VSD patients with larger shunts (Qp/Qs&lt;2) as Group III. Besides, seven tetralogy of fallot (TOF) with shunt (Qp/Qs>4) infants were classified as the Group IV. A
nonradioactive DIG-RNA probe detection system, western blotting and immunohistochemistry were used to detect the gene expression levels and protein products of IGF-I and IGF-IR in the right atrium samples of VSD infants. The relative protein levels of IGF-I were 0.96±0.05, 0.43±0.03,
0.15±0.04, 0.12±0.03 and IGF-IR were 0.80±0.08, 0.57±0.03, 0.38±0.02, 0.24±0.04 in the right atrium of 4 group patients. The relative mRNA levels of IGF-I were 0.95±0.01, 0.41±0.03, 0.29±0.05, 0.15±0.01 and IGF-IR were 0.85±0.05, 0.56±0.03, 0.17±0.01, 0.18±0.01, respectively.
There was a significantly greater but more gradual decrease in protein levels and in mRNA levels of IGF-I and IGF-IR in Group II ( p&lt;0.05), Group III and IV (&lt;0.01) than in Group I. The results of immunohistochemistry also demonstrated a similar decrease in VSD patients. In addition, the decrease of mRNA and protein levels in IGF-I/
IGF-IR of VSD patients show related to the saturation of oxygen in the right atrium and the ratio of systolic right ventricular pressure to left ventricular pressure. We further confirmed the down regulation of IGF-I/IGF-IR in cardiac tissue of VSD infants and the decrease to be
associated with shunt magnitude and the severity of hypoxemia in the cardiac chamber of VSD.

目錄
壹、中文摘要 8
貳、英文摘要 11
參、前言與背景介紹 14
一、高鉀離子心臟麻醉劑 14
二、心肌細胞之計劃性凋亡 14
三、類胰島素生長因子 19
肆、研究動機 22
伍、研究材料與方法 23
一、新生兒心臟組織檢體收集 23
二、冠狀動脈繞道搭橋手術病患檢體收集 23
三、細胞培養 24
四、蛋白濃度測定 25
五、西方墨點法 25
六、siRNA 轉殖 26
七、MMP 活性分析 27
八、RNA 的萃取 27
九、Reverse Transcription/Polymerase Chain Reaction 28
十、IGF-I mRNA探針之製備 29
十一、Dot blotting 30
十二、組織切片 30
十三、TUNEL 細胞凋亡分析 31
十四、DAPI 細胞螢光染色分析 32
陸、實驗結果 34
高鉀離子心臟麻醉灌流液誘發心肌細胞凋亡及心臟纖維
化相關機制之探討
ㄧ、接受CABG 的CAD 病人右心房檢體具有大量
細胞凋亡之現象 34
二、高鉀離子心臟麻醉灌流液與KCl 溶液誘發H9c2
心肌細胞凋亡 34
三、高鉀離子心臟麻醉灌流液或KCl 溶液誘發CAD
病人右心房心肌細胞與H9c2 心肌細胞大量表
現促凋亡蛋白 34
四、接受CABG的CAD病人右心房檢體具有IGF-I
與IGF-IR表現量增加之現象 35
五、高鉀離子心臟麻醉灌流液和KCl溶液誘發H9c2
心肌細胞開啟IGF-I與IGF-IR基因並促進大量
表現IGF-I與IGF-IR蛋白 36
六、高鉀離子心臟麻醉灌流液開啟心臟纖維化訊息
途徑 36
七、高鉀離子心臟麻醉灌流液和KCl溶液誘發MMP-2
和MMP-9活性與表現量增加 37
八、MEK1 siRNA抑制高鉀離子心臟麻醉灌流液所
誘發uPA, MMP-2, MMP-9, Sp-1和CTGF的表現
量增加 38
類胰島素生長因子及其接受體基因在心室中隔缺損嬰兒
之心肌組織表現下降之探討
九、臨床個案之特徵及相關資料 39
十、利用Western blotting 比較各組間IGFI 與IGFIR
蛋白含量 40
十一、利用double-Y Plot software 比較各組間IGFI
與IGFIR 蛋白含量與病患病情嚴重的相互關
係 40
十二、利用dot blot 分析各組IGFI 與IGFIR 的mRNA
expression 41
十三、利用immunocytochemistry分析各組IGFI與IGFIR
的蛋白含量 42
柒、討論 43
捌、圖表說明 48
Figure 1. Cell apoptosis detection by TUNEL in right atrium
tissues of CABG patients and in high KCl-treated
H9c2 cells 50
Figure 2. Activation of Bad, caspase-3 and cytochrome c in
right atrium tissues of CABG patients and in high
KCl-treated H9c2 cells 52
Figure 3. Detection of IGF-1 and IGF-1R expression in right
atrium tissues of CABG patients 54
Figure 4. Detection of IGF-1 and IGF-1R expression in H9c2
cardiomyoblast cells treated with cardioplegic
solution and KCl solution 56
Figure 5. Detection of proteins related to cardiomyocyte
survival and cardiac fibrosis pathways in right
atrium tissues of CABG patients 59
Figure 6. Upregulation and/or activation of uPA, MMP-2,
MMP-9, Sp-1 and CTGF in postcardioplegic right
atriums, in H9c2 cells and neonatal cardiac fibroblasts
during cardioplegic solution treatment 61
Table 1. Characteristics of subjects in study 62
Figure 7. Western blotting analysis for insulin-like grow
factor-I, insulin-like growth factor-I receptor, and
α-tubulin in the right atrium of 4 group patients 63
Figure 8. Double-Y plot software to compare the tendency
of IGF-I or IGF-IR protein levels and RA SaO2,
RAP, RVP/LVP in each groups 64
Figure 9. Dot blotting analysis for IGF-I mRNA, IGF-IR
mRNA, and 18S rRNA in the right atrium of four
group patients 65
Figure 10. Immunocytochemistry of the right atrium in one
infant of each group 66
玖、參考文獻 67
拾、已發表之論文抽印本 75

1.Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322-1326
2.Aebert H, Cornelius T, Birnbaum DE, Siegel AV, Riegger GA, Schunkert H (1997) Induction of early immediate genes and programmed cell death following cardioplegic arrest in human hearts. Eur J Cardiothorac Surg 12:261-267
3.Aragno M, Mastrocola R, Alloatti G, Vercellinatto I, Bardini P, Geuna S, Catalano MG, Danni O, Boccuzzi G (2008) Oxidative stress triggers cardiac fibrosis in the heart of diabetic rats. Endocrinology 149:380-388
4.Bernstein D, Teitel D, Sidi D, Heymann MA, Rudolph AM (1987) Redistribution of regional blood flow and oxygen delivery in experimental cyanotic heart disease in newborn lambs. Pediatr Res 22:389-393
5.Buerke M, Murohara T, Skurk C, Nuss C, Tomaselli K, Lefer AM (1995) Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. Proc Natl Acad Sci U S A 92:8031-8035
6.Butt AJ, Firth SM, Baxter RC (1999) The IGF axis and programmed cell death. Immunol Cell Biol 77:256-262
7.Chambers DJ (1999) Polarization and myocardial protection. Curr Opin Cardiol 14:495-500
8.Chen HS, Shan YX, Yang TL, Lin HD, Chen JW, Lin SJ, Wang PH (2005) Insulin deficiency downregulated heat shock protein 60 and IGF-1 receptor signaling in diabetic myocardium. Diabetes 54:175-181
9.Chen YF, Wu SC, Huang CH, Pan PC, Lee CS, Lin CC (2001) Morphometric identification of luminal narrowing of myocardial capillaries after cardioplegic arrest. Ann Thorac Surg 71:243-248
10.Datta SR, Brunet A, Greenberg ME (1999) Cellular survival: a play in three Akts. Genes Dev 13:2905-2927
11.Dean RG, Balding LC, Candido R, Burns WC, Cao Z, Twigg SM, Burrell LM (2005) Connective tissue growth factor and cardiac fibrosis after myocardial infarction. J Histochem Cytochem 53:1245-1256
12.Downward J (1999) How BAD phosphorylation is good for survival. Nat Cell Biol 1:E33-35
13.Florini JR, Ewton DZ, Coolican SA (1996) Growth hormone and the insulin-like growth factor system in myogenesis. Endocr Rev 17:481-517
14.Franke TF, Cantley LC (1997) Apoptosis. A Bad kinase makes good. Nature 390:116-117
15.Gross A, McDonnell JM, Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899-1911
16.Huang CY, Kasai M, Buetow DE (1998) Extremely-rapid RNA detection in dot blots with digoxigenin-labeled RNA probes. Genet Anal 14:109-112
17.Isgaard J, Tivesten A, Friberg P, Bengtsson BA (1999) The role of the GH/IGF-I axis for cardiac function and structure. Horm Metab Res 31:50-54
18.Ito H, Hiroe M, Hirata Y, Tsujino M, Adachi S, Shichiri M, Koike A, Nogami A, Marumo F (1993) Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation 87:1715-1721
19.Janicki JS, Brower GL, Gardner JD, Chancey AL, Stewart JA, Jr. (2004) The dynamic interaction between matrix metalloproteinase activity and adverse myocardial remodeling. Heart Fail Rev 9:33-42
20.Kajstura J, Fiordaliso F, Andreoli AM, Li B, Chimenti S, Medow MS, Limana F, Nadal-Ginard B, Leri A, Anversa P (2001) IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes 50:1414-1424
21.Kelekar A, Thompson CB (1998) Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 8:324-330
22.Kim S, Iwao H (2000) Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 52:11-34
23.Kothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K, McGarry TJ, Kirschner MW, Koths K, Kwiatkowski DJ, Williams LT (1997) Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science 278:294-298
24.Kuo WW, Chu CY, Wu CH, Lin JA, Liu JY, Hsieh YH, Ueng KC, Lee SD, Hsieh DJ, Hsu HH, Chen LM, Huang CY (2005) Impaired IGF-I signalling of hypertrophic hearts in the developmental phase of hypertension in genetically hypertensive rats. Cell Biochem Funct 23:325-331
25.Lang C, Sauter M, Szalay G, Racchi G, Grassi G, Rainaldi G, Mercatanti A, Lang F, Kandolf R, Klingel K (2008) Connective tissue growth factor: a crucial cytokine-mediating cardiac fibrosis in ongoing enterovirus myocarditis. J Mol Med 86:49-60
26.Lee SD, Chen LM, Kuo WW, Shu WT, Kuo WH, Huang EJ, Tsai CC, Li PC, Liu JY, Chen TH, Huang CY (2006) Serum insulin-like growth factor-axis and matrix metalloproteinases in patients with rheumatic arthritis or rheumatic heart disease. Clin Chim Acta 367:62-68
27.LeRoith D, Werner H, Beitner-Johnson D, Roberts CT, Jr. (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 16:143-163
28.Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491-501
29.Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479-489
30.Li Q, Li B, Wang X, Leri A, Jana KP, Liu Y, Kajstura J, Baserga R, Anversa P (1997) Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. J Clin Invest 100:1991-1999
31.Li YY, McTiernan CF, Feldman AM (2000) Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovasc Res 46:214-224
32.Luo X, Budihardjo I, Zou H, Slaughter C, Wang X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94:481-490
33.Mauney MC, Kron IL (1995) The physiologic basis of warm cardioplegia. Ann Thorac Surg 60:819-823
34.Mori SS, Fujii GG, Ishida HH, Tomari SS, Matsuura AA, Yoshida KK (2003) Atrial flutter after coronary artery bypass grafting: proposed mechanism as illuminated by independent predictors. Ann Thorac Cardiovasc Surg 9:50-56
35.Nissley P, Lopaczynski W (1991) Insulin-like growth factor receptors. Growth Factors 5:29-43
36.O''Connor R, Kauffmann-Zeh A, Liu Y, Lehar S, Evan GI, Baserga R, Blattler WA (1997) Identification of domains of the insulin-like growth factor I receptor that are required for protection from apoptosis. Mol Cell Biol 17:427-435
37.Ohnishi H, Oka T, Kusachi S, Nakanishi T, Takeda K, Nakahama M, Doi M, Murakami T, Ninomiya Y, Takigawa M, Tsuji T (1998) Increased expression of connective tissue growth factor in the infarct zone of experimentally induced myocardial infarction in rats. J Mol Cell Cardiol 30:2411-2422
38.Park GH, Buetow DE (1991) Genes for insulin-like growth factors I and II are expressed in senescent rat tissues. Gerontology 37:310-316
39.Parrizas M, LeRoith D (1997) Insulin-like growth factor-1 inhibition of apoptosis is associated with increased expression of the bcl-xL gene product. Endocrinology 138:1355-1358
40.Parrizas M, Saltiel AR, LeRoith D (1997) Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3''-kinase and mitogen-activated protein kinase pathways. J Biol Chem 272:154-161
41.Rainio P, Kaukoranta PK, Sormunen R, Juvonen T, Peuhkurinen KJ (1998) Ultrastructural changes in myocardium during mild hypothermic retrograde blood cardioplegia. Scand Cardiovasc J 32:353-359
42.Reed JC (1998) Bcl-2 family proteins. Oncogene 17:3225-3236
43.Reed JC (1997) Double identity for proteins of the Bcl-2 family. Nature 387:773-776
44.Rosse T, Olivier R, Monney L, Rager M, Conus S, Fellay I, Jansen B, Borner C (1998) Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 391:496-499
45.Rudel T, Bokoch GM (1997) Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. Science 276:1571-1574
46.Sakahira H, Enari M, Nagata S (1998) Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391:96-99
47.Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB, Fesik SW (1997) Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275:983-986
48.Scarabelli TM, Pasini E, Ferrari G, Ferrari M, Stephanou A, Lawrence K, Townsend P, Chen-Scarabelli C, Gitti G, Saravolatz L, Latchman D, Knight RA, Gardin JM (2004) Warm blood cardioplegic arrest induces mitochondrial-mediated cardiomyocyte apoptosis associated with increased urocortin expression in viable cells. J Thorac Cardiovasc Surg 128:364-371
49.Schendel SL, Azimov R, Pawlowski K, Godzik A, Kagan BL, Reed JC (1999) Ion channel activity of the BH3 only Bcl-2 family member, BID. J Biol Chem 274:21932-21936
50.Schmitt JP, Schroder J, Schunkert H, Birnbaum DE, Aebert H (2002) Role of apoptosis in myocardial stunning after open heart surgery. Ann Thorac Surg 73:1229-1235
51.Stenbog EV, Hjortdal VE, Ravn HB, Skjaerbaek C, Sorensen KE, Hansen OK (2000) Improvement in growth, and levels of insulin-like growth factor-I in the serum, after cavopulmonary connections. Cardiol Young 10:440-446
52.Tappy L, Fujita-Yamaguchi Y, LeBon TR, Boden G (1988) Antibodies to insulin-like growth factor I receptors in diabetes and other disorders. Diabetes 37:1708-1714
53.Thanbichler M, Bock A (2002) The function of SECIS RNA in translational control of gene expression in Escherichia coli. Embo J 21:6925-6934
54.Tsai TP, Yu JM, Wu YL, Huang CY, Chen FL (2002) Change of serum growth factors in infants with isolated ventricular defect undergoing surgical repair. Ann Thorac Surg 73:1765-1768; discussion 1769
55.von Lewinski D, Voss K, Hulsmann S, Kogler H, Pieske B (2003) Insulin-like growth factor-1 exerts Ca2+-dependent positive inotropic effects in failing human myocardium. Circ Res 92:169-176
56.Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC (1999) Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science 284:339-343
57.Werner H, Le Roith D (1997) The insulin-like growth factor-I receptor signaling pathways are important for tumorigenesis and inhibition of apoptosis. Crit Rev Oncog 8:71-92
58.Yamamura T, Otani H, Nakao Y, Hattori R, Osako M, Imamura H (2001) IGF-I differentially regulates Bcl-xL and Bax and confers myocardial protection in the rat heart. Am J Physiol Heart Circ Physiol 280:H1191-1200
59.Yuan J (1997) Transducing signals of life and death. Curr Opin Cell Biol 9:247-251
60.Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405-413



QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文