北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学民航临床医学院  > 学位论文
学科主题: 内科学
题名:
内脂素在冠状动脉粥样硬化性心脏病发病中的作用研究
作者: 田俊媛
答辩日期: 2009-05-12
导师: 季汉华
专业: 内科学
授予单位: 北京大学
授予地点: 北京大学民航临床医学院
学位: 硕士
关键词: 内脂素 冠状动脉粥样硬化性心脏病 炎症 脂肪组织
其他题名: The research about the role of the plasma visfatin in coronary atherosclerotic heart disease
分类号: R541.4
摘要:

背景 目前,越来越多的研究证明,血管壁内皮的慢性炎症反应在冠心病的发生发展中起到重要的作用。冠心病患者内皮中多种炎症因子水平升高。脂肪组织不仅单纯具有储存能量的作用,同时能分泌多种介质参与炎症反应,这些分泌型因子称为Adipocytokine。内脂素是新近发现的一种由脂肪细胞分泌的因子,广泛分布于人体内,在内脏脂肪组织中分布最多,故称为内脂素,即内脏脂肪素。它具有类胰岛素作用,并能参与脂代谢调节过程。然而,血浆内脂素水平与冠心病的病理生理过程及与病变程度的关系仍不十分清楚。

目的:观察冠心病患者血浆中内脂素及肿瘤坏死因子的变化,分析内脂素与冠心病危险因子、肿瘤坏死因子、冠状动脉病变程度的相关性,探讨内脂素在冠心病发病中的可能作用及与病变程度的关系。

方法 采用酶连免疫法测定52例冠心病患者和28例正常对照组的空腹内脂素水平;收集冠心病患者病历相关资料;统计分析。

结果 冠心病患者血内脂素水(5.275±3.39ng/ml高于对照组2.884±1.46ng/ml,多因素分析显示血内脂素水平与冠心病的发病无明显相关。多元线性回归分析发现血浆内脂素与肿瘤坏死因子、血糖、白细胞、中性粒细胞、纤维蛋白原相关。

结论 冠心病患者血浆内脂素水平高于正常组,多因素分析显示血浆内脂素水平与冠心病的发病无显著相关,多元线性回归分析发现血浆内脂素水平与肿瘤坏死因子水平之间存在正相关关系。血浆内脂素水平与代表冠心病病变程度的Gensini评分呈正相关(r=0.371P=0.04)。未发现内脂素与腰臀比、体重指数以及血脂之间有显著相关性。

英文摘要:

1.     Hideki Katagiri, Tetsuya Yamada and Yoshitomo Oka. Consisting of Humoral and Neuronal Signals:Adiposity and Cardiovascular Disorders: Disturbance of the Regulatory System. Circ. Res. 2007,101:27-39

2.     Alexander R. Moschen, Arthur Kaser,Visfatin, an Adipocytokine with Proinflammatory and Immunomodulating Properties The Journal of Immunology. 2007, 178: 1748–1758.

3.     Berg AH, Lin Y, Lisanti MP, Scherer PE. Adipocyte differentiation induces dynamic changes in NF-kappaB expression and activity. Am J Physiol Endocrinol Metab. 2004,287:E1178–E1188.

4.     Halle M, Persson PB. Role of leptin and leptin receptor in inflammation. Am J Physiol Regul Integr Comp Physiol. 2003,284:R760–R762.77.

5.     Sanchez-Margalet V, Martin-Romero C, Santos-Alvarez J, Goberna R,Najib S, Gonzalez-Yanes C. Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action. Clin Exp Immunol. 2003,133:11–19.

6.     Shamsuzzaman AS, Winnicki M, Wolk R, Svatikova A, Phillips BG,Davison DE, Berger PB, Somers VK. Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation.2004,109:2181–2185.

7.     Ren J. Leptin and hyperleptinemia—from friend to foe for cardiovascularfunction. J Endocrinol. 2004,181:1–10.

8.     Fukuhara A,Matsuda M,Nishizawa M,etal Visfatin:a protein secreted by visceral fat that mimics the effects of insulin. Science,2005,307(5708):426-430.

9.     Adeghate E.Visfatin: structure, function and relation to diabetes mellitus and other dysfunctions.  Curr Med Chem. 2008,15(18):1851-62

10. Jia SH, Li Y, Parodo J, etal. PreB cell colonyenhancing factor inhibits neutrophil apop tosis in experimental inflammation and clinical sep sis. J Clin Invest. 2004, 113 (9) : 13181327

11. Ognjanovic S, Bao S, Yamamoto SY. Genomic organization of the gene coding for human p reBcell colony enhancing factor and expression in human fetal membranes. Mol Endocrinol. 2001, 26 (2) :107117

1.     Curat CA, Wegner V, Sengenès V. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin, 2006, 49 (4) : 744 - 747 Epub 2006, 23.

2.     Tuva B. Dahl, MSc; Arne Yndestad, MSc. Increased Expression of Visfatin in Macrophages of Human Unstable Carotid and Coronary Atherosclerosis Possible Role in Inflammation and Plaque Destabilization. Circulation 2007, 115: 972 -980

3.     Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology. 2004,145:2273–228.

4.     Maeda, N., I. Shimomura, K. Kishida, H. Nishizawa, M. Matsuda, H. Nagaretani,N. Furuyama, H. Kondo, M. Takahashi, Y. Arita, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat. Med. 2002,8: 731–737.

5.     Wolf, A. M., D. Wolf, H. Rumpold, B. Enrich, and H. Tilg. 2004. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes.Biochem. Biophys. Res. Commun. 323: 630–635.

6.     La Cava, A., G. Matarese. The weight of leptin in immunity. Nat. Rev.Immunol.2004, 4: 371–379.

7.     Cayatte AJ, Palacino JJ, Horten K, Cohen RA. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb. 1994,14:753–759.

8.     Hamon M, Vallet B, Bauters C, Wernert N, McFadden EP, Lablanche JM, Dupuis B, Bertrand ME. Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendotheliumdependent acetylcholine-induced relaxation after arterial injury. Circulation.1994,90:1357–1362.

9.     Liao JK, Bettmann MA, Sandor T, Tucker JI, Coleman SM, Creager MA. Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis. Circ Res. 1991,68:1027–1034.

10. Radomski MW, Palmer RM, Moncada S, An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci U S A. 1990,87:5193–5197.

11. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromocyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 1989;83: 1774–1777.

12. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulatorof leukocyte adhesion. Proc Natl Acad Sci U S A. 1991,88: 4651–4655.

13. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med. 1992,326:242–250.

14. Cybulsky MI, Gimbrone MA Jr. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991,251:788–791.

15. evilacqua MP, Nelson RM. Endothelial-leukocyte adhesion molecules in inflammation and metastasis. Thromb Haemost. 1993,70:152–154.

16. Speir E, Modali R, Huang ES, Leon MB, Shawl F, Finkel T, Epstein SE Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science. 1994,265:391–394.

17. Leinonen M, Linnanmaki E, Mattila K, Nieminen MS, Valtonen V, Leirisalo-Repo M, Saikku P. Circulating immune complexes containing chlamydial lipopolysaccharide in acute myocardial infarction. Microb Pathog. 1990,9:67–73.

18. Hotamisligil G. Inflammatory pathways and insulin action. Int J Obes Relat Metab Disord. 2003,(suppl 3):S53–S55.

19. Ridker PM, Rifai N, PfefferM, et al. Elevation of Tumor Necrosis Factor2alpha and Inercased Risk of Recurrent Coronary Events afterMyocardial Infarction . Circulation, 2000, 101 (18) : 2149-2153

20. Hohlfeld T, Klemm P,Mermannc T, et al. TheContribution of TumorNecrosis Factor and Endothelin-1 to the Increase of Coronary Resistance in Hearts from Rats Treated with Endotoxin. Br J pharmacol, 1995, 116 ( 8 ) : 3309-3315.

1.     Gryglewski RJ. Modulation of the Pharmacological Action of Nitroua sodilation by Methyene Blue and Pyocyanin. Br J pharmacol, 1991, 106 (4) : 8382845.

2.     Amento EP, Ehsani N, Palmer H, et al. Cytokines and Growth Factors Positively and Negatively Regulate Interstitial Collagen Gene Expression in Human Vascular SmoothMuscle Cells. Arterioscler Thromb, 1991, 11 (5) : 1223-1230.

3.     Brown D I, HibbsMS, KearneyM, et al. Identification of 922KD Gelatinase in Human Coronary Atherostitrotic Lesions. Circulation, 1995, 91 (8) : 2125-2131.

4.     Miyao Y, Yasur H,Ogawe H, et al. Elevated IL-6 Levels in Patients with Acute Myocardial Infarction . Am Heart J , 1993, 126 (6) : 1299-1303.

1.     Schreyer SA, Vick CM, LeBoeuf RC. Loss of lymphotoxin-alpha but not tumor necrosis factor-alpha reduces atherosclerosis in mice. J Biol Chem. 2002,277:12364 –12368.

2.     Li W, Iyer S, Lu L, Buelow R, Fung JJ, Rao AS, Woo J, Qian S.Attenuation of aortic graft arteriosclerosis by systemic administration of Allotrap peptide RDP58. Transpl Int. 2003,16:849–856.

3.     Schreyer SA, Peschon JJ, LeBoeuf RC. Accelerated atherosclerosis in mice lacking tumor necrosis factor receptor p55. J Biol Chem. 1996,271:26174 –26178.

4.     Khanna D, McMahon M, Furst DE. Anti-tumor necrosis factor alpha therapy and heart failure: what have we learned and where do we go from here? Arthritis Rheum. 2004,50:1040 –1050.

5.     Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003,112:1796 –1808.

6.     Xu H, Uysal KT, Becherer JD, Arner P, Hotamisligil GS. Altered tumor necrosis factor-alpha (TNF-alpha) processing in adipocytes and increased expression of transmembrane TNF-alpha in obesity. Diabetes.2002,51:1876 –1883.

7.     Tsigos C, Kyrou I, Chala E, Tsapogas P, Stavridis JC, Raptis SA,Katsilambros N. Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity. Metabolism. 1999,48:1332–1335

8.     Bhagat K, Vallance P. Inflammatory cytokines impairs endothelium dependent dilatation in human veins in vivo. Circulation. 1997,96: 3042–3047.

9.     Sethi JK,Vidal-Puig A.Visfatin:the missing link between intra-abdominal obesity and diabetes?  Trend Mol Med.2005,11(8):344-347.

语种: 中文
出处: http://xuewei.bjmu.edu.cn/simpsearch.action?keyword=内脂素在冠状动脉粥样硬化性心脏病发病中的作用研究&dbid=72
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/105450
Appears in Collections:北京大学民航临床医学院_学位论文

Files in This Item:

There are no files associated with this item.


作者单位: 北京大学民航临床医学院

Recommended Citation:
田俊媛. 内脂素在冠状动脉粥样硬化性心脏病发病中的作用研究[D]. 北京大学民航临床医学院. 北京大学. 2009.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[田俊媛]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[田俊媛]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace