严重脓毒症患者VEGF水平及病原学研究
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摘要
血管内皮生长因子(VEGF)是直接作用于血管内皮细胞的生长因子,具有增加微血管通透性等功能。其在脓毒症中的作用国外已展开研究,国内研究尚不多。
目的:
本研究通过检测严重脓毒症患者血清VEGF水平,探讨VEGF与脓毒症疾病严重程度及预后的关系;了解脓毒症的病原菌现状及体外耐药性,为临床提供治疗依据。
方法:
1.收集2006年7月～2007年10月某医院急救中心和ICU收治的严重脓毒症患者的临床资料及发病后1、3、7天生命体征、血常规、肝肾功能、电解质、血气分析、LAC和C-RP,计算APACHEII评分。根据患者28天转归不同分为生存组和死亡组。2.采用ELISA方法检测患者发病后1、3、7天血清VEGF水平,留取健康体检者血清检测VEGF水平并设为对照组。3.收集可疑感染部位标本经常规法进行菌株鉴定,纸片法和微量肉汤稀释法进行药敏试验。4.统计学方法:定性资料采用x~2检验,定量资料采用t或F检验,VEGF水平与年龄、HR、MAP、WBC、PLT、ALB、LAC、C-RP、及APACHEII评分的相关性研究采用双变量相关分析,应用非条件Logistic回归分析对上述数值进行统计学处理,得出影响患者预后的死亡危险因素,对危险因素绘制ROC曲线。
结果:
1.本研究共收集严重脓毒症病例29例,男18例,女11例。其中生存组16例,死亡组13例,病死率为44.8%,男女病死率无统计学差异(44.4%vs45.5%,p＞0.05)。其感染病因依次为重症肺炎(24.14%)、导管相关性血流感染(17.24%)、急性肾盂肾炎(10.34%),其他(48.3%)2.应用ELISA方法检测血清VEGF水平,结果显示对照组VEGF水平为78.77±8.15pg/ml,生存组1、3、7天VEGF水平分别为210.47±59.40pg/ml、161.79±32.58pg/ml、85.33±12.13pg/ml,其峰值出现在第一天,随病程进展VEGF水平逐渐下降,第7天与对照组比较无统计学差异(p＞0.05)。死亡组1、3、7天VEGF水平分别为324.12±44.35 pg/ml、185.40±30.92 pg/ml、273.32±55.23 pg/ml,明显高于对照组,其峰值亦出现在第一天,随病程进展第7天VEGF水平下降不明显,第7天与对照组比较仍明显升高(p＜0.01)。死亡组与生存组相比,第1、7天死亡组VEGF水平高于生存组,存在统计学差异(t=-5.717,p＜0.01和t=-10.604,p＜0.01),第3天无统计学差异(t=-1.888,p＞0.05)。3.经双变量相关分析结果显示,严重脓毒症患者VEGF水平与APACHEII评分呈正相关(r=0.510,p＜0.01),与血小板呈负相关(r=-0.221,p＜0.05),与HR、MAP、WBC、ALB、LAC、C-RP及年龄无相关性(p＞0.05)。将患者年龄、APACHEII评分、HR、MAP、WBC、PLT、LAC、ALB、C-RP及VEGF水平纳入非条件Logistic回归分析,结果显示VEGF水平、APACHEII评分、年龄为影响患者预后的死亡危险因素(p＜0.05)。4.本研究共分离出病原菌93株,全部分离株中G~-菌47株,G~+菌27株,真菌19株。主要病原菌依次为铜绿假单胞菌12株、金黄色葡萄球菌12株、大肠杆菌10株、白假丝酵母菌9株,铜绿假单胞菌对头胞吡肟、环丙沙星、亚胺培南的耐药率均在60%以上,金黄色葡萄球菌均对万古霉素敏感,MRSA分离率为83.3%。19株真菌对抗真菌药的耐药率均在20%以下。
结论:
1.严重脓毒症患者VEGF水平升高峰值出现在第1天,随病程进展生存组VEGF水平逐渐下降,第7天接近正常。死亡组第7天VEGF水平下降不明显,有升高趋势。
2.VEGF水平与APACHEII评分呈正相关,与血小板呈负相关。
3.VEGF水平、APACHEII评分、年龄是严重脓毒症患者的死亡危险因素。
4.本研究分离的病原菌以铜绿假单胞菌、金黄色葡萄球菌、大肠杆菌为主,呈现对常用抗生素的多重耐药性。
Vascular endothelial growth factor is a growth factor that acts at vascular endothelial cells,with the function of increasing microvascular permeability.Its function in sepsis has been put so much attention abroad,yet there is not so much at home.
Objective:
Vascular endothelial growth factor is a growth factor that acts at vascular endothelial cells,with the function of increasing microvascular permeability.Its function in sepsis has been put so much attention abroad,yet there is not so much at home.The aim of the study was to examine VEGF levels in severe sepsis serum, show its significance to the prognosis.To know about the situation of the pathogen and its drug resistance outside the body,meanwhile provide a foundation for therapy.
Methods:
1.Enroll the severe sepsis patients basic informations who were hospitalized in emergency center and ICU of some hospital from July 2006 to October 2007.Record clinical and laboratory dates on the 1~(st),3~(rd),7~(th)day,and calculate APACHEII score.Divide the patients into survival group and death group according to 28 day lasting.2.Examine the VEGF levels on the 1~(st),3~(rd),7~(th)day by ELISA.3.Collected the pathogens of the severe sepsis patients and MIC antibacterial activity.4.statistical methods:Qualitative dates analysed by x~2-test.Quantitative dates analysed by t-test or F-test.Do the bivariate analysis between the VEGF levels and other dates as age,HR,MAP,PLT,WBC,ALB,C-RP,LAC.Apply binary logistic regression to do statistical dealings.Select the risk factors and draw the ROC curre.
Results:
1.There are 29 severe sepsis patients including 18 male ones and 11 female ones.16 cases survived and 13 ones died.The case fatality rate is 44.8%.The pathogenies are severe pneumonia(24.14%),catheter-relatedinfection(17.24%), acutepyelonephritis(10.34%),others(48.3%)2.Apply ELISA the VEGF levels in the control group is 78.77±8.15pg/ml,in the survival group on the 1~(st),3~(rd),7~(th)day are 210.47±59.40pg/ml,161.79±32.58pg/ml,85.33±12.13pg/ml,the peak value appeared on the 1~(st)day.the VEGF levels decreased with the development of the disease.There has not statistical difference between control group and survival group on the 7~(th)day(p＞0.05).In the death group,VEGF levels on the 1~(st),3~(rd),7~(th)day are 324.12±44.35pg/ml、185.40±30.92pg/ml、273.32±55.23pg/ml,all of which are higher than the control group,the peak value also appeared on the 1~(st)day,but it decreased unconspicuously on the 7~(th)day,it is obviously higher than the control group (p＜0.01).VEGF levels in death group on the 1~(st),7~(th)day are higher than survival group,which has statistical difference(t=-5.717,p＜0.01 and t=-10.604,p＜0.01).On the 3~(rd)day the difference is unconspicuously(t=-1.888,p＞0.05).3.Through bivariate analysis,VEGF levels has positive relation with APACHEII score (r=0.510,p＜0.01),negative relation with PLT(r=-0.221,p＜0.05),and no relation with other parameters(p＞0.05).Bringing age,APACHEIIscore,HR,MAP,WBC,PLT,C-RP, ALB and VEGF levels into unconditional Logistic regression,the results show the VEGF levels,APACHEII score and age are risk factors that can influence the prognosis(p＜0.05).4.In this study 93 pathogens are separated.Of 93 clinical isolated,the Gram-negative organism accounted for 47,the Gram-positive organism 27,fungi 19.The main pathogens are Pseudomons aeruginosa(12),staphyloccus aureus(12),E.coli(10),cavdida pneumonia(9),Pseudomonas aeruginosa drug resistance rate to cefepime,ciprofloxacin,imipenem are all higher than 60%.All the staphyloccus aureus are susceptive to vancomycin,the separation rate of MRSA is 83.3%.The 19 fungi drug resistance rate to antifungi medicine are all lower than 20%.
Conclusions:
VEGF levels in severe sepsis patients are higher than the control group on the 1~(st) day.It decreases in the course of disease in the survival group,but it decreases unconspicuously in death group.VEGF levels is positively related with APACHEII score and negatively related with PLT.VEGF levels,APACHEII score and age are risk factors for death.In this study pseudomonas aeruginosa,staphyloccus aureus, E.coli are the main pathogens,which are mutil-drug resistance.
目的:
本研究通过检测严重脓毒症患者血清VEGF水平,探讨VEGF与脓毒症疾病严重程度及预后的关系;了解脓毒症的病原菌现状及体外耐药性,为临床提供治疗依据。
方法:
1.收集2006年7月～2007年10月某医院急救中心和ICU收治的严重脓毒症患者的临床资料及发病后1、3、7天生命体征、血常规、肝肾功能、电解质、血气分析、LAC和C-RP,计算APACHEII评分。根据患者28天转归不同分为生存组和死亡组。2.采用ELISA方法检测患者发病后1、3、7天血清VEGF水平,留取健康体检者血清检测VEGF水平并设为对照组。3.收集可疑感染部位标本经常规法进行菌株鉴定,纸片法和微量肉汤稀释法进行药敏试验。4.统计学方法:定性资料采用x~2检验,定量资料采用t或F检验,VEGF水平与年龄、HR、MAP、WBC、PLT、ALB、LAC、C-RP、及APACHEII评分的相关性研究采用双变量相关分析,应用非条件Logistic回归分析对上述数值进行统计学处理,得出影响患者预后的死亡危险因素,对危险因素绘制ROC曲线。
结果:
1.本研究共收集严重脓毒症病例29例,男18例,女11例。其中生存组16例,死亡组13例,病死率为44.8%,男女病死率无统计学差异(44.4%vs45.5%,p＞0.05)。其感染病因依次为重症肺炎(24.14%)、导管相关性血流感染(17.24%)、急性肾盂肾炎(10.34%),其他(48.3%)2.应用ELISA方法检测血清VEGF水平,结果显示对照组VEGF水平为78.77±8.15pg/ml,生存组1、3、7天VEGF水平分别为210.47±59.40pg/ml、161.79±32.58pg/ml、85.33±12.13pg/ml,其峰值出现在第一天,随病程进展VEGF水平逐渐下降,第7天与对照组比较无统计学差异(p＞0.05)。死亡组1、3、7天VEGF水平分别为324.12±44.35 pg/ml、185.40±30.92 pg/ml、273.32±55.23 pg/ml,明显高于对照组,其峰值亦出现在第一天,随病程进展第7天VEGF水平下降不明显,第7天与对照组比较仍明显升高(p＜0.01)。死亡组与生存组相比,第1、7天死亡组VEGF水平高于生存组,存在统计学差异(t=-5.717,p＜0.01和t=-10.604,p＜0.01),第3天无统计学差异(t=-1.888,p＞0.05)。3.经双变量相关分析结果显示,严重脓毒症患者VEGF水平与APACHEII评分呈正相关(r=0.510,p＜0.01),与血小板呈负相关(r=-0.221,p＜0.05),与HR、MAP、WBC、ALB、LAC、C-RP及年龄无相关性(p＞0.05)。将患者年龄、APACHEII评分、HR、MAP、WBC、PLT、LAC、ALB、C-RP及VEGF水平纳入非条件Logistic回归分析,结果显示VEGF水平、APACHEII评分、年龄为影响患者预后的死亡危险因素(p＜0.05)。4.本研究共分离出病原菌93株,全部分离株中G~-菌47株,G~+菌27株,真菌19株。主要病原菌依次为铜绿假单胞菌12株、金黄色葡萄球菌12株、大肠杆菌10株、白假丝酵母菌9株,铜绿假单胞菌对头胞吡肟、环丙沙星、亚胺培南的耐药率均在60%以上,金黄色葡萄球菌均对万古霉素敏感,MRSA分离率为83.3%。19株真菌对抗真菌药的耐药率均在20%以下。
结论:
1.严重脓毒症患者VEGF水平升高峰值出现在第1天,随病程进展生存组VEGF水平逐渐下降,第7天接近正常。死亡组第7天VEGF水平下降不明显,有升高趋势。
2.VEGF水平与APACHEII评分呈正相关,与血小板呈负相关。
3.VEGF水平、APACHEII评分、年龄是严重脓毒症患者的死亡危险因素。
4.本研究分离的病原菌以铜绿假单胞菌、金黄色葡萄球菌、大肠杆菌为主,呈现对常用抗生素的多重耐药性。
Vascular endothelial growth factor is a growth factor that acts at vascular endothelial cells,with the function of increasing microvascular permeability.Its function in sepsis has been put so much attention abroad,yet there is not so much at home.
Objective:
Vascular endothelial growth factor is a growth factor that acts at vascular endothelial cells,with the function of increasing microvascular permeability.Its function in sepsis has been put so much attention abroad,yet there is not so much at home.The aim of the study was to examine VEGF levels in severe sepsis serum, show its significance to the prognosis.To know about the situation of the pathogen and its drug resistance outside the body,meanwhile provide a foundation for therapy.
Methods:
1.Enroll the severe sepsis patients basic informations who were hospitalized in emergency center and ICU of some hospital from July 2006 to October 2007.Record clinical and laboratory dates on the 1~(st),3~(rd),7~(th)day,and calculate APACHEII score.Divide the patients into survival group and death group according to 28 day lasting.2.Examine the VEGF levels on the 1~(st),3~(rd),7~(th)day by ELISA.3.Collected the pathogens of the severe sepsis patients and MIC antibacterial activity.4.statistical methods:Qualitative dates analysed by x~2-test.Quantitative dates analysed by t-test or F-test.Do the bivariate analysis between the VEGF levels and other dates as age,HR,MAP,PLT,WBC,ALB,C-RP,LAC.Apply binary logistic regression to do statistical dealings.Select the risk factors and draw the ROC curre.
Results:
1.There are 29 severe sepsis patients including 18 male ones and 11 female ones.16 cases survived and 13 ones died.The case fatality rate is 44.8%.The pathogenies are severe pneumonia(24.14%),catheter-relatedinfection(17.24%), acutepyelonephritis(10.34%),others(48.3%)2.Apply ELISA the VEGF levels in the control group is 78.77±8.15pg/ml,in the survival group on the 1~(st),3~(rd),7~(th)day are 210.47±59.40pg/ml,161.79±32.58pg/ml,85.33±12.13pg/ml,the peak value appeared on the 1~(st)day.the VEGF levels decreased with the development of the disease.There has not statistical difference between control group and survival group on the 7~(th)day(p＞0.05).In the death group,VEGF levels on the 1~(st),3~(rd),7~(th)day are 324.12±44.35pg/ml、185.40±30.92pg/ml、273.32±55.23pg/ml,all of which are higher than the control group,the peak value also appeared on the 1~(st)day,but it decreased unconspicuously on the 7~(th)day,it is obviously higher than the control group (p＜0.01).VEGF levels in death group on the 1~(st),7~(th)day are higher than survival group,which has statistical difference(t=-5.717,p＜0.01 and t=-10.604,p＜0.01).On the 3~(rd)day the difference is unconspicuously(t=-1.888,p＞0.05).3.Through bivariate analysis,VEGF levels has positive relation with APACHEII score (r=0.510,p＜0.01),negative relation with PLT(r=-0.221,p＜0.05),and no relation with other parameters(p＞0.05).Bringing age,APACHEIIscore,HR,MAP,WBC,PLT,C-RP, ALB and VEGF levels into unconditional Logistic regression,the results show the VEGF levels,APACHEII score and age are risk factors that can influence the prognosis(p＜0.05).4.In this study 93 pathogens are separated.Of 93 clinical isolated,the Gram-negative organism accounted for 47,the Gram-positive organism 27,fungi 19.The main pathogens are Pseudomons aeruginosa(12),staphyloccus aureus(12),E.coli(10),cavdida pneumonia(9),Pseudomonas aeruginosa drug resistance rate to cefepime,ciprofloxacin,imipenem are all higher than 60%.All the staphyloccus aureus are susceptive to vancomycin,the separation rate of MRSA is 83.3%.The 19 fungi drug resistance rate to antifungi medicine are all lower than 20%.
Conclusions:
VEGF levels in severe sepsis patients are higher than the control group on the 1~(st) day.It decreases in the course of disease in the survival group,but it decreases unconspicuously in death group.VEGF levels is positively related with APACHEII score and negatively related with PLT.VEGF levels,APACHEII score and age are risk factors for death.In this study pseudomonas aeruginosa,staphyloccus aureus, E.coli are the main pathogens,which are mutil-drug resistance.
引文
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37.Edmond MB,Wallace SE,McClish DK,et al.Nosocomial bloodst ream infections in United States hospitals:a there-year analysis.Clin Infect Dis,1999,29(2):239-244.
38.韩佳音,何彩娟,冯瑞萍,等.798例住院患者医院感染调查与分析[J].中华医院感染学杂志,2004,14(9):986-988.
39.金美娟,李秀红,邢旺兴.236株铜绿假单胞菌感染的临床分析[J].中华医院感染学杂志,2005,15(3):348-350.
40.Bone RC.Gram-positive orgamisms.Arch Intern Med,1994,154:26-34
41.黄伯高,袁克俭,胡桂芳,等.1998～2000年954株烧伤感染菌耐药调查分析.上海第二医科大学学报,2002,22:551-553.
42.Alvarez-Lerma F,Palomar M,Leon C,et al.Fungal colonization and/or infection in intensive care units1Multicenter study of 1562 patients[J].Med Clin(Barc),2003,121(5):161
43.Kaml W,Lin J D.Management of systemic candidal infections in the intensive care unit[J].Am J Health Syst Pharm,2002,59(1):33-41.
44.文细毛,任南,徐秀华,等.全国医院感染监控网医院感染病原菌分布及耐药性分析[J].中华医院感染学杂志,2002,12(4):241-244.
45.冯霞飞,叶进燕,周小洁等.ICU医院内深部真菌感染临床分析[J].中国微生态学杂志,2006,18(5):389-390
46.Peman J,Canton E,Gobemado M,et al.Epidemiology and antifungal susceptibility of Candida species isolated from blood:results of a -year multicent restudy in Spain[J].Eur J Clin Microbiol Infect Dis,2005,24(1):23-30.
1. Ferrara N , Henzel W J .Pituitary follicular cells secerte anovel heparin-binding grawth factor specific vascular endothelial cells[J].Biochem eiophys Res Commun,1989,161(2):851
2. Mura M , Santos CC ,Stewart D ,etal.Vascular endothelial growth factor and related molecules in acute lung injury [J ].Appl Physiol ,2004 ,97(5):1605-1617.
3. Hwada A ,Yoshioka Y ,Iwabchi K ,et al .VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells[J] .Thorax ,2003 ,58(4):328-332
4. Ferrara N, Gerber HP , Lecouter J . The biology of VEGF and its receptors[J]. Nat Med ,2003 ,9(6):669-676
5. Dpangelo G,Beck H ,Danner S ,et al. Placenta growth factor [J]. Proc Natl Acad Sei USA, 1995 ,92:6374
6. Prttersson A, Nagy TA, Brown LF , et al. Heterogeneity of angiogenic response induced indifferent nomal adult tissues by vascular permeability factor/vascular endothelial growth factor [J]. Clin Invest ,2000 ,80(1) :99-102
7. Fong GH, Rossant J , GertsensteiuM , et al. Role of the Flt-I receptor tyrosine regulation the assembly of vasular endothelium[J]. Nature, 1995, 376: 66-70
8. Senger D ,Galli SJ, Dvorak AM ,et al.Tumor cells secrete a vascular permeability factor which prmotes ascites fluid accumulation [J]. Science, 1983,219(4):983
9. Lazarours DF,Shou M,Scheinowitz M,et al.Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury[J].Circulation,1996,94: 1074-1082
10. Murohara T, Horowitz JR, Silverm M.Vascular endothelial growth factoroV PE enhances vascular permeability via nitric oxide and prostacyclin[J]. Circulation, 1998, 97: 99-107
11. Semenza G.Signal transduction to hypoxia-inducible factor[J].Biochem Pharmacol, 2002,64(5-6):993-998
12. Wen FQ, Liu X , Manda W,et al.Th2 Cytokine-enhanced and TGF-beta-enhanced vascular endothelial growth factor production by cultured human airway smoth muscle cells is attenuated by INF-gamma and corticosteroids[J].Allergy Clin Immunol,2003,111(6):1307-1318
13.Dvorak HF.Expressioellsn of vascular permeability factor/vascular endothelial growth factor by human granulose and the calutein cells:role in corpus luteum development[J].Am J Pathol,1995,146(2):1029-1039
14.Tian X,Song S,Wu J,et al.Vascular endothelial growth factor:acting as an autocrinegrowth factor for human gastric adenocarcinoma cell MGC803[J].Biochem Biophys Res Commun,2001,286(3):505-512.
15.Gille H,Kowalski J,Li B,et al.Analysis of biological effect s and signaling properties of Flt-1(VEGFR-1)and KDR(VEGFR-2).A reassessment using novel receptor specific vascular endothelial growth factor mutants[J].Biol Chem,2001,276(5):3222-3230.
16.Gershenwald J E,Fidler IJ.Cancer.Targeting lymphatic metastasis[J].Science,2002,296(5574):1811-1812.
17.Yamaguchi R,Yano H,Iemura A et al.Exp ression of vascular endothelial growth factor in human hepatocellular carcinoma[J].Hepatology,1998,28:68-77
18.郭占文.非小细胞肺癌患者放疗前后血清血管内皮生长因子变化的研究[J].中国免疫学杂志,2002,18(11):807-809
19.Hao Z,Franklin B.How do cells sense oxygen[J]Science,2001,292(5516):449-451
20.Gu JW,Adair TH.Hpoxia-induced expression of VEGF is reversible in myocardial vascular smooth muscle cells.Am J Physiol,1997,273(2P2):H628
21.Damert A,Machein M,Breier G,et al.Up-regulation of vascular endothelial growth factor expression in a rat glioma is a conferred by two distinct hypoxia-driven mechanisms[J].Cancer Res,1997,57:3860
22.Schultz A,Lavie L,Hochberg I,et al.Interindividual heterogeneity in the hypoxic regulation of VEGF:significance for the development of the coronary artery collateral circulation[J].Circulation,1999,100:547-552.
23.Seko Y,Imai Y,Snznki S,et al.Serum levels of vascular endothelial growth factor in patients with acute myocardial infarction undergoing reperfusion therapy[J].Clin Sci Colch,1997,92(5):453
24. Banai S, Jaklitsh MT, shou M , et al. Angiogenic induced enhancement of co llatral blood flow to ischem ic myocardium by vascular endothelial growth factor in dogs[J]. Circulation, 1994, 89:2183
25. Van BE, Tio FO , Couffinhal T, et al. Stent endo thelialization time course, impact of local cathetar delivery feasiblity of recombinant protein administration and response to cytokine expedition[J]. Circulation, 1997, 95 (2): 438
26. Van BE, Tio FO , chen D, et al. Passivatiou of metallic stents afear arterial gene transfer of VEGF 165 inhibits thrombus for mation and intimal thickening[J]. Am coll cardiol, 1997, 29: 1371
27. Walder CE,Errett CJ,Bunting S,et al.Vasculal endothelial growth factor augments muscleblood flow and in a rabbit model of chronic hindlimb ischemia[J]. Cardiovasc Pharmacol, 1996,27:91-98
28. Asai K , Kanazawa H , Kamoi H ,et al .Increased levels of vascular endothelil growth factor in induced sputum in asthmatic patients[J].Clin Exp Allergy ,2003 ,33(5):595-599
29. Yoo Y , Koh YY ,Kang HM ,et al. Sputum eosinophil counts and eosinophil cationic protein levels in cough-variant asthma and in classic asthma , and their relationships to airway hypersensitivity or maximal airway response to methacholine[J]. Allergy ,2004,59(10): 1055-1062.
30. Ancelin M ,Chollet-Martin S , Herve MA, et al. Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in extravascular tissue via an autocrine amplification mechanism[J] .Lab Invest ,2004,84(4):502-512
31. Lee TH, Avraham H, Lee SH, et al. Vascular endothelial growth factor modulates neutrophil transendothelial migration via up-regulation of interleukin -8 in human brain microvascular endothelial cells[J].Biol Chem,2002,277(12): 10445-10451.
32. Nakasone T , Hanashiro K , Nakamura M ,et al.Mast cell-derived VEGF enhances the passage of IgE FE-3 through the rat aortic endothelial cell monolayer[J]. Int Arch Allergy Immunol,2002,129(1):76-85
33. Hirst SJ, Twort CH , Lee TH. Differential effects of extracellular matrix proteins on human airway smooth muscle cell proliferation and phenotype. Am J Respir Cell Mol Biol ,2000,23(3):335-344.
34. Shapiro NI ,Howell M ,Talmor D.A blueprint for a sepsis protocol .Acad Emerg Med, 2005,12(4):352-359
35. Martin GS ,Mannino DM, Eaton S ,et al . The epidemiology of sepsis in the United States from 1979 through 2000.N Eng Med ,2003,348 1546-1554.
36. Nolan A, Weiden MD, Thurston G, et al .Vascular endothelial growth factor block adereduces plasma cytokines in a murinemodel of polymicro bia sepsis[J].Inflammation, 2004,28(5):271-278.
37. Van der Flier M,van Leeuwen HJ ,van Kessel KP ,et al. Plasma vascular endothelial growth factor in severe sepsis [J]. Shock ,2005 ,23 (1) :35-38.
38. Pickkers P ,Sprong T , Eij K, et al.Vascular endothelial growth factors increased during the first 48 hours of human septic shock and correlates with vascular permeability[J]. Shock ,2005 ,24(6) :508-512.
39. Yano K ,Liaw PC,Mullington JM,etal.Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality [J]. Exp Med ,2006,203(6) :1447-1458
2.Martin GS,Mannino DM,Eaton S,et al.The epidemiology of sepsis in the United States from 1979 through 2000.N Eng Med,2003,348:1546-1554.
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7.Ferrara N,Gerber HP,Lecouter J.The Biology of VEGF and its receptors[J].Nat Med,2003,9(6):669-676.
8.Nolan A,Weiden MD,Thurston G,et al.Vascular endothelial growth factor block adereduces plasma cytokines in a murinemodel of polymicro bia sepsis [J].Inflammation,2004,28(5):271-278.
9.Pickkers P,Sprong T,Eij K,et al.Vascular endothelial growth factors increased during the first 48 hours of human septic shock and correlates with vascular permeability[J].Shock,2005,24(6):508-512.
10.Yano K,Liaw PC,Mullington JM,etal.Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality[J].Exp Med,2006,203(6):1447-1458
11.Vincent JL,Sakr Y,Sprung CL,etal.Sepsis in European intensive care units:results of the SOAP study[J].Crit Care Med,2006,34(2):344-353.
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20.Zierner LS,Koch CJ,Mzity A,et al.Hypoxia and VEGF mRNA expression in human tumors[J].Neoplasia,2001,3(6):500-508
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22.Dente CJ,Steffes CP,Speyer CL,et al.Pericytes augment the capillary barrier in vitro cocultures[J].Res 2001,97:85-91.
23.Lydia Donoghue MD,James G,Tyburski MD,et al.Vascular endothelial growth factor modulates contractile response in microvascular lung pericytes[J].The American Journal of Surgery,2006,191:349-352.
24.郭文璐,徐仑.血管内皮生长因子的研究现状及其与脓毒症的关系[J].国际儿科学杂志,2007,34(2):110-113.
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31.Homma H,Hoy E,Xu DZ,et al.The female intestine ismore resistant than the male intestine to gut injury and inflammation when subjected to conditions associated with shock states[J].Am J Physiol,2005,288(3):G466-472
32.常文秀,曹书华,王勇强,等.性别因素在多器官功能障碍综合征中的意义[J].中国急救医学 2007,27(6):492-494
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35.张诗海,曾邦雄.85例中心静脉导管相关感染分析[J].中华医院感染学杂志,2002,12(2):89.
36.邹琳,俞森洋.导管相关感染的病原学及相关危险因素[J].中华医院感染学杂志,2005,15(4):405
37.Edmond MB,Wallace SE,McClish DK,et al.Nosocomial bloodst ream infections in United States hospitals:a there-year analysis.Clin Infect Dis,1999,29(2):239-244.
38.韩佳音,何彩娟,冯瑞萍,等.798例住院患者医院感染调查与分析[J].中华医院感染学杂志,2004,14(9):986-988.
39.金美娟,李秀红,邢旺兴.236株铜绿假单胞菌感染的临床分析[J].中华医院感染学杂志,2005,15(3):348-350.
40.Bone RC.Gram-positive orgamisms.Arch Intern Med,1994,154:26-34
41.黄伯高,袁克俭,胡桂芳,等.1998～2000年954株烧伤感染菌耐药调查分析.上海第二医科大学学报,2002,22:551-553.
42.Alvarez-Lerma F,Palomar M,Leon C,et al.Fungal colonization and/or infection in intensive care units1Multicenter study of 1562 patients[J].Med Clin(Barc),2003,121(5):161
43.Kaml W,Lin J D.Management of systemic candidal infections in the intensive care unit[J].Am J Health Syst Pharm,2002,59(1):33-41.
44.文细毛,任南,徐秀华,等.全国医院感染监控网医院感染病原菌分布及耐药性分析[J].中华医院感染学杂志,2002,12(4):241-244.
45.冯霞飞,叶进燕,周小洁等.ICU医院内深部真菌感染临床分析[J].中国微生态学杂志,2006,18(5):389-390
46.Peman J,Canton E,Gobemado M,et al.Epidemiology and antifungal susceptibility of Candida species isolated from blood:results of a -year multicent restudy in Spain[J].Eur J Clin Microbiol Infect Dis,2005,24(1):23-30.
1. Ferrara N , Henzel W J .Pituitary follicular cells secerte anovel heparin-binding grawth factor specific vascular endothelial cells[J].Biochem eiophys Res Commun,1989,161(2):851
2. Mura M , Santos CC ,Stewart D ,etal.Vascular endothelial growth factor and related molecules in acute lung injury [J ].Appl Physiol ,2004 ,97(5):1605-1617.
3. Hwada A ,Yoshioka Y ,Iwabchi K ,et al .VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells[J] .Thorax ,2003 ,58(4):328-332
4. Ferrara N, Gerber HP , Lecouter J . The biology of VEGF and its receptors[J]. Nat Med ,2003 ,9(6):669-676
5. Dpangelo G,Beck H ,Danner S ,et al. Placenta growth factor [J]. Proc Natl Acad Sei USA, 1995 ,92:6374
6. Prttersson A, Nagy TA, Brown LF , et al. Heterogeneity of angiogenic response induced indifferent nomal adult tissues by vascular permeability factor/vascular endothelial growth factor [J]. Clin Invest ,2000 ,80(1) :99-102
7. Fong GH, Rossant J , GertsensteiuM , et al. Role of the Flt-I receptor tyrosine regulation the assembly of vasular endothelium[J]. Nature, 1995, 376: 66-70
8. Senger D ,Galli SJ, Dvorak AM ,et al.Tumor cells secrete a vascular permeability factor which prmotes ascites fluid accumulation [J]. Science, 1983,219(4):983
9. Lazarours DF,Shou M,Scheinowitz M,et al.Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury[J].Circulation,1996,94: 1074-1082
10. Murohara T, Horowitz JR, Silverm M.Vascular endothelial growth factoroV PE enhances vascular permeability via nitric oxide and prostacyclin[J]. Circulation, 1998, 97: 99-107
11. Semenza G.Signal transduction to hypoxia-inducible factor[J].Biochem Pharmacol, 2002,64(5-6):993-998
12. Wen FQ, Liu X , Manda W,et al.Th2 Cytokine-enhanced and TGF-beta-enhanced vascular endothelial growth factor production by cultured human airway smoth muscle cells is attenuated by INF-gamma and corticosteroids[J].Allergy Clin Immunol,2003,111(6):1307-1318
13.Dvorak HF.Expressioellsn of vascular permeability factor/vascular endothelial growth factor by human granulose and the calutein cells:role in corpus luteum development[J].Am J Pathol,1995,146(2):1029-1039
14.Tian X,Song S,Wu J,et al.Vascular endothelial growth factor:acting as an autocrinegrowth factor for human gastric adenocarcinoma cell MGC803[J].Biochem Biophys Res Commun,2001,286(3):505-512.
15.Gille H,Kowalski J,Li B,et al.Analysis of biological effect s and signaling properties of Flt-1(VEGFR-1)and KDR(VEGFR-2).A reassessment using novel receptor specific vascular endothelial growth factor mutants[J].Biol Chem,2001,276(5):3222-3230.
16.Gershenwald J E,Fidler IJ.Cancer.Targeting lymphatic metastasis[J].Science,2002,296(5574):1811-1812.
17.Yamaguchi R,Yano H,Iemura A et al.Exp ression of vascular endothelial growth factor in human hepatocellular carcinoma[J].Hepatology,1998,28:68-77
18.郭占文.非小细胞肺癌患者放疗前后血清血管内皮生长因子变化的研究[J].中国免疫学杂志,2002,18(11):807-809
19.Hao Z,Franklin B.How do cells sense oxygen[J]Science,2001,292(5516):449-451
20.Gu JW,Adair TH.Hpoxia-induced expression of VEGF is reversible in myocardial vascular smooth muscle cells.Am J Physiol,1997,273(2P2):H628
21.Damert A,Machein M,Breier G,et al.Up-regulation of vascular endothelial growth factor expression in a rat glioma is a conferred by two distinct hypoxia-driven mechanisms[J].Cancer Res,1997,57:3860
22.Schultz A,Lavie L,Hochberg I,et al.Interindividual heterogeneity in the hypoxic regulation of VEGF:significance for the development of the coronary artery collateral circulation[J].Circulation,1999,100:547-552.
23.Seko Y,Imai Y,Snznki S,et al.Serum levels of vascular endothelial growth factor in patients with acute myocardial infarction undergoing reperfusion therapy[J].Clin Sci Colch,1997,92(5):453
24. Banai S, Jaklitsh MT, shou M , et al. Angiogenic induced enhancement of co llatral blood flow to ischem ic myocardium by vascular endothelial growth factor in dogs[J]. Circulation, 1994, 89:2183
25. Van BE, Tio FO , Couffinhal T, et al. Stent endo thelialization time course, impact of local cathetar delivery feasiblity of recombinant protein administration and response to cytokine expedition[J]. Circulation, 1997, 95 (2): 438
26. Van BE, Tio FO , chen D, et al. Passivatiou of metallic stents afear arterial gene transfer of VEGF 165 inhibits thrombus for mation and intimal thickening[J]. Am coll cardiol, 1997, 29: 1371
27. Walder CE,Errett CJ,Bunting S,et al.Vasculal endothelial growth factor augments muscleblood flow and in a rabbit model of chronic hindlimb ischemia[J]. Cardiovasc Pharmacol, 1996,27:91-98
28. Asai K , Kanazawa H , Kamoi H ,et al .Increased levels of vascular endothelil growth factor in induced sputum in asthmatic patients[J].Clin Exp Allergy ,2003 ,33(5):595-599
29. Yoo Y , Koh YY ,Kang HM ,et al. Sputum eosinophil counts and eosinophil cationic protein levels in cough-variant asthma and in classic asthma , and their relationships to airway hypersensitivity or maximal airway response to methacholine[J]. Allergy ,2004,59(10): 1055-1062.
30. Ancelin M ,Chollet-Martin S , Herve MA, et al. Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in extravascular tissue via an autocrine amplification mechanism[J] .Lab Invest ,2004,84(4):502-512
31. Lee TH, Avraham H, Lee SH, et al. Vascular endothelial growth factor modulates neutrophil transendothelial migration via up-regulation of interleukin -8 in human brain microvascular endothelial cells[J].Biol Chem,2002,277(12): 10445-10451.
32. Nakasone T , Hanashiro K , Nakamura M ,et al.Mast cell-derived VEGF enhances the passage of IgE FE-3 through the rat aortic endothelial cell monolayer[J]. Int Arch Allergy Immunol,2002,129(1):76-85
33. Hirst SJ, Twort CH , Lee TH. Differential effects of extracellular matrix proteins on human airway smooth muscle cell proliferation and phenotype. Am J Respir Cell Mol Biol ,2000,23(3):335-344.
34. Shapiro NI ,Howell M ,Talmor D.A blueprint for a sepsis protocol .Acad Emerg Med, 2005,12(4):352-359
35. Martin GS ,Mannino DM, Eaton S ,et al . The epidemiology of sepsis in the United States from 1979 through 2000.N Eng Med ,2003,348 1546-1554.
36. Nolan A, Weiden MD, Thurston G, et al .Vascular endothelial growth factor block adereduces plasma cytokines in a murinemodel of polymicro bia sepsis[J].Inflammation, 2004,28(5):271-278.
37. Van der Flier M,van Leeuwen HJ ,van Kessel KP ,et al. Plasma vascular endothelial growth factor in severe sepsis [J]. Shock ,2005 ,23 (1) :35-38.
38. Pickkers P ,Sprong T , Eij K, et al.Vascular endothelial growth factors increased during the first 48 hours of human septic shock and correlates with vascular permeability[J]. Shock ,2005 ,24(6) :508-512.
39. Yano K ,Liaw PC,Mullington JM,etal.Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality [J]. Exp Med ,2006,203(6) :1447-1458