寒潮诱发高血压大鼠脑卒中与脑血管NF-κB和ICAM-1的表达关系
|
摘要
目的通过对肾血管性高血压大鼠(renovascular hypertensive rats, RHR)不同血压水平对脑动脉核转录因子-κB(nuclear factor kappa-B, NF-κB)和细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)的影响和不同血压水平下寒潮对脑血管内皮NF-κB和ICAM-1的影响的研究。初步探讨寒潮诱发脑卒中的机制以及了解NF-κB和ICAM-1对易卒中状态的影响。
方法应用双肾双夹法复制RHR模型,术后12周形成稳定高血压后,正常血压组(假手术组)与RHR组各分为寒潮和非寒潮两大组;RHR组又分为160mmHg～199mmHgRHR、200mmHg～219mmHgRHR、≥220mmHg RHR3个亚组;正常血压组及RHR各亚组12只大鼠。发生脑卒中者被剔出卒中前状态的分析,另外补充处理大鼠,保证免疫组化每亚组各有6只无卒中大鼠。寒潮组置于人工气候箱中,温度设置以22℃12小时,4℃12小时为1天循环,共3天。非寒潮组置于温度22℃的人工气候箱共3天。在人工气候箱处理前后测量体重、血压以寒潮3天、出现偏瘫症状或意识障碍、死亡为研究终点,在研究终点将大鼠灌注后断头取脑(除死亡鼠),作以下处理:每亚组随机取6只大鼠用于免疫组化,每只大鼠张随机取10张切片作免疫组化检测血管内皮的NF-κB和ICAM-1的蛋白表达,其余切片作HE染色,了解是否有卒中病灶。
结果1.各组血压比较:正常血压鼠经人工气候箱处理(寒潮或非寒潮)后血压均升高, RHR经寒潮后血压均较寒潮前降低,差异有统计学意义,P﹤0.05。
2.脑卒中情况:正常血压组无脑卒中发生。饲养过程中RHR组有8只大鼠出现脑卒中症状;人工气候箱处理后,RHR寒潮组的脑卒中发生率为22.2%(8/36),非寒潮组的脑卒中发生率为2.7%(1/36),两者差异有统计学意义(P<0.05)。
3.脑血管的NF-κB和ICAM-1的蛋白(免疫组化)表达:两因素方差分析表明:不同血压水平大鼠脑动脉的NF-κB和ICAM-1表达不同, P<0.01;非寒潮组与寒潮组的表达不同, P<0.01;血压与处理方法有交互作用。进一步分析表明:1)剔除脑卒中的各血压组大鼠经人工气候箱处理后NF-κB和ICAM-1蛋白表达变化趋势一致如下:在<220mmHg血压组,寒潮组的蛋白表达比非寒潮组高,P<0.05;在≥220mmHg血压亚组,寒潮组的上述指标比非寒潮组有降低,P<0.01;在非寒潮组,蛋白表达均随血压升高而升高,P<0.01。在寒潮组,上述指标在<220 mmHg时均随血压升高而升高,P<0.05。2)脑卒中后的血浆NF-κB和ICAM-1蛋白表达均比非卒中组高:a)脑梗死组比非脑卒中组和脑出血组高,差异有统计学意义,P﹤0.05,P﹤0.01;b)脑出血组与非脑卒中组脑血管的NF-κB和ICAM-1比较差异均有统计学意义,P﹤0.05。
结论NF-κB和ICAM-1的表达变化可能在高血压脑卒中和寒潮诱发脑卒中的过程中起着重要作用。
Objective We have employed the rats with levels of different blood pressure to study the activity changes of NF-κB and ICAM-1 in endothelial dysfunction under ACE. In addition, 2k2c RHR with different levels of high blood pressure were examined to evaluate the contribution of endothelial cell adhesion molecules on the induction of stroke under the cold exposure.
Methods Two-kidney-two-clip RHR were used in the present study. The sham-operated rats were undergone the same experimental procedures except for placement of clip, they (n= 24) served as normotensive controls. Normal sham-operated rats and 2k2c RHR were randomly assigned into 2 groups: ACE and non-ACE. Each group was further divided into 4 sub-groups according to their SBP (after 2k2c operation before the ACE treatment):①Sham-operated control group, BP<140mmHg,②mild hypertensive group, BP of 160-200mmHg,③moderate hypertensive group, BP of 200-220mmHg, and④severe hypertensive group, BP≥220mmHg. To establish the ACE and non-ACE treatment, the RHR were housed individually in a modified intelligent artificial climate cabinet. The ACE was designed as 3 cycles of 12 h light of 22℃and 12 h dark of 4℃. The non-ACE group was kept at 22℃throughout the experiment. Movement of limbs and consciousness of the rats were recorded twice daily during ACE and non-ACE treatment. Systolic BP (SBP), body weight were measured before and after ACE or non-ACE treatment. Afterwards, rat brains were removed quickly and then sectioned into 2.0-mm-thick coronal sections. 5.0-μm-thick paraffin sections or frozen sections from bregma section were stained with immunohistochemistry. Other sections were stained with HE to observe whether stroke occurred.
Results 1.Blood pressures in different group generally decreased to some extent after ACE treatment compared with those before ACE treatment. For the sham-operated control rats (BP<140 mmHg), no rat has developed stroke under either the non-ACE or ACE conditions. In contrast, the 2k2c RHR as a whole exhibited 2.7% (1/36) incidence of stroke under the non-ACE conditions. 2.Moreover, ACE treatment further increased the stoke incidence to 22.2% (8/36, P < 0.01).3. NF-κB and ICAM-1 were measured in rats of stroke vulnerability but without stroke showed a similar trend as follows:the expression of NF-κB and ICAM-1 were different in rats of different blood pressure level, P<0.01;and them were different in rats of ACE and non-ACE, P<0.01;there are interaction between blood pressure level and different deal methods. a)In Bp <220mmHg subgroup, both indexes were elevated after ACE compared with those before ACE P<0.05; On the other hand, both the indexes in Bp≥220mmHg subgroup decreased to some extent after ACE treatment compared with those before ACE,P<0.05. b) Among rats with not-ACE treatment, there is a positive association between high blood pressure and both indexes. Among rats with not-ACE treatment, this positive association can also be seen in rats with Bp <220mmHg, however, Both indexes decreased dramatically in rats with Bp≥220mmHg compared with those with Bp <220mmHg, P<0.05. In addition, Both indexes in rats without stroke were different from those in rats with stroke.
Conclusions Up-regulative expression of NF-κB and ICAM-1 may play a role in the onset of cerebral apoplexy in intracranial artery when RHR Induced by Artificial Cold Exposure.
方法应用双肾双夹法复制RHR模型,术后12周形成稳定高血压后,正常血压组(假手术组)与RHR组各分为寒潮和非寒潮两大组;RHR组又分为160mmHg～199mmHgRHR、200mmHg～219mmHgRHR、≥220mmHg RHR3个亚组;正常血压组及RHR各亚组12只大鼠。发生脑卒中者被剔出卒中前状态的分析,另外补充处理大鼠,保证免疫组化每亚组各有6只无卒中大鼠。寒潮组置于人工气候箱中,温度设置以22℃12小时,4℃12小时为1天循环,共3天。非寒潮组置于温度22℃的人工气候箱共3天。在人工气候箱处理前后测量体重、血压以寒潮3天、出现偏瘫症状或意识障碍、死亡为研究终点,在研究终点将大鼠灌注后断头取脑(除死亡鼠),作以下处理:每亚组随机取6只大鼠用于免疫组化,每只大鼠张随机取10张切片作免疫组化检测血管内皮的NF-κB和ICAM-1的蛋白表达,其余切片作HE染色,了解是否有卒中病灶。
结果1.各组血压比较:正常血压鼠经人工气候箱处理(寒潮或非寒潮)后血压均升高, RHR经寒潮后血压均较寒潮前降低,差异有统计学意义,P﹤0.05。
2.脑卒中情况:正常血压组无脑卒中发生。饲养过程中RHR组有8只大鼠出现脑卒中症状;人工气候箱处理后,RHR寒潮组的脑卒中发生率为22.2%(8/36),非寒潮组的脑卒中发生率为2.7%(1/36),两者差异有统计学意义(P<0.05)。
3.脑血管的NF-κB和ICAM-1的蛋白(免疫组化)表达:两因素方差分析表明:不同血压水平大鼠脑动脉的NF-κB和ICAM-1表达不同, P<0.01;非寒潮组与寒潮组的表达不同, P<0.01;血压与处理方法有交互作用。进一步分析表明:1)剔除脑卒中的各血压组大鼠经人工气候箱处理后NF-κB和ICAM-1蛋白表达变化趋势一致如下:在<220mmHg血压组,寒潮组的蛋白表达比非寒潮组高,P<0.05;在≥220mmHg血压亚组,寒潮组的上述指标比非寒潮组有降低,P<0.01;在非寒潮组,蛋白表达均随血压升高而升高,P<0.01。在寒潮组,上述指标在<220 mmHg时均随血压升高而升高,P<0.05。2)脑卒中后的血浆NF-κB和ICAM-1蛋白表达均比非卒中组高:a)脑梗死组比非脑卒中组和脑出血组高,差异有统计学意义,P﹤0.05,P﹤0.01;b)脑出血组与非脑卒中组脑血管的NF-κB和ICAM-1比较差异均有统计学意义,P﹤0.05。
结论NF-κB和ICAM-1的表达变化可能在高血压脑卒中和寒潮诱发脑卒中的过程中起着重要作用。
Objective We have employed the rats with levels of different blood pressure to study the activity changes of NF-κB and ICAM-1 in endothelial dysfunction under ACE. In addition, 2k2c RHR with different levels of high blood pressure were examined to evaluate the contribution of endothelial cell adhesion molecules on the induction of stroke under the cold exposure.
Methods Two-kidney-two-clip RHR were used in the present study. The sham-operated rats were undergone the same experimental procedures except for placement of clip, they (n= 24) served as normotensive controls. Normal sham-operated rats and 2k2c RHR were randomly assigned into 2 groups: ACE and non-ACE. Each group was further divided into 4 sub-groups according to their SBP (after 2k2c operation before the ACE treatment):①Sham-operated control group, BP<140mmHg,②mild hypertensive group, BP of 160-200mmHg,③moderate hypertensive group, BP of 200-220mmHg, and④severe hypertensive group, BP≥220mmHg. To establish the ACE and non-ACE treatment, the RHR were housed individually in a modified intelligent artificial climate cabinet. The ACE was designed as 3 cycles of 12 h light of 22℃and 12 h dark of 4℃. The non-ACE group was kept at 22℃throughout the experiment. Movement of limbs and consciousness of the rats were recorded twice daily during ACE and non-ACE treatment. Systolic BP (SBP), body weight were measured before and after ACE or non-ACE treatment. Afterwards, rat brains were removed quickly and then sectioned into 2.0-mm-thick coronal sections. 5.0-μm-thick paraffin sections or frozen sections from bregma section were stained with immunohistochemistry. Other sections were stained with HE to observe whether stroke occurred.
Results 1.Blood pressures in different group generally decreased to some extent after ACE treatment compared with those before ACE treatment. For the sham-operated control rats (BP<140 mmHg), no rat has developed stroke under either the non-ACE or ACE conditions. In contrast, the 2k2c RHR as a whole exhibited 2.7% (1/36) incidence of stroke under the non-ACE conditions. 2.Moreover, ACE treatment further increased the stoke incidence to 22.2% (8/36, P < 0.01).3. NF-κB and ICAM-1 were measured in rats of stroke vulnerability but without stroke showed a similar trend as follows:the expression of NF-κB and ICAM-1 were different in rats of different blood pressure level, P<0.01;and them were different in rats of ACE and non-ACE, P<0.01;there are interaction between blood pressure level and different deal methods. a)In Bp <220mmHg subgroup, both indexes were elevated after ACE compared with those before ACE P<0.05; On the other hand, both the indexes in Bp≥220mmHg subgroup decreased to some extent after ACE treatment compared with those before ACE,P<0.05. b) Among rats with not-ACE treatment, there is a positive association between high blood pressure and both indexes. Among rats with not-ACE treatment, this positive association can also be seen in rats with Bp <220mmHg, however, Both indexes decreased dramatically in rats with Bp≥220mmHg compared with those with Bp <220mmHg, P<0.05. In addition, Both indexes in rats without stroke were different from those in rats with stroke.
Conclusions Up-regulative expression of NF-κB and ICAM-1 may play a role in the onset of cerebral apoplexy in intracranial artery when RHR Induced by Artificial Cold Exposure.
引文
1.Field TS,Hill MD.Weather,Chinook,and stroke occurrence[J].Stroke, 2002, 33(7):1751
2.Pan W,Li L,Tsai M.Temperature extremes and mortality from coronary heart disease and cerebral infarction in elderly chinese[J]. Lancet,1995;345: 353-355
3.Hong YC,Rha JH, Lee JT,et al.Ischemic stroke associated with decrease in temperature[J].Epidemiology,2003,14(4):473.
4.黄如训,苏镇培主编.脑卒中[M].人民卫生出版社(北京). 2001年第1版:11.
5.Ronen Sumagin,Ingrid H. A role for ICAM-1 in maintenance of leukocyte- endothelial cell rolling interactions in inflamed arterioles.2007, 293: H2786-H2798
6.Alvaro LC,FreijoMM,Sadaba F.Inflammatory mechanisms, arteriosclerosis and ischemic stroke :clinical data and persperctives [J]. RevNeurol.2002,35:452.
7. Simundic AM, Basic V, Topic E, demarin V. et al .Soluble adhesion molecules in acute ischemic stroke[J]. Clin Invest Med. 2004 Apr;27(2):86-92.
8. Tanne D, Haim M, Boyko V, et al. Soluble intercellular adhesion molecule-1 and risk of future ischemic stroke: A nested case-control study from the bezafibrate infarction prevention (bip) study cohort[J]. Stroke. 2002;33:2182-2186.
9.李敬诚,周华东,张猛,等.脑梗死患者血清可溶性细胞间黏附分子水平变化及其临床意义.中国神经免疫学和神经病学杂志[J].2007 ,14:57-58.
10.Collina T. Biology of disease:Endothelial nuclear factor-κB and initiation of atherosclerotic lesion[J]. Lab Invest ,1993 ;68(5) :499～508.
11.赵峰,室田诚逸,森田育男,等.NF-κB与疾病[J].生命科学,2001, 1(31):11
12.李建军,李庚山. NF-κB与心血管疾病[J].国外医学分子生物学分册, 1999, 21: 123-126
13. Zeng J, Zhang Y, Mo J, Su Z, Huang R. Two-kidney, two clip renovascular hypertensive rats can be used as stroke-prone rats[J]. Stroke. 1998;29:1708-1713; discussion 1713-1704.
14.解龙昌,黄如训,李常新,等.人工寒潮促发脑卒中的实验研究[J].中国神经精神疾病杂志,2004,30(3):198-201.
15.Fardon NJ , Wilkinson R , Thomas TH . Rapid fusion of granules with neutrophil cell membranes in hypertensive patients may increase vascular damage [J] . A m J Hypertension ,2001 ,14 :927
16.Caimi G,Presti RL ,Carollo C ,et al. Polymorphonuclear integrins,membrane fluidity , and cytosolic Ca2+ content after activation in essential hypertension[J] . Hypertension ,2000 ,36 (5) :813
17.Falk E , Shah PK, Fuster V. Coronary plaque disruption[J] . Circulation , 1995 , 92 :657.
18.吴进寿,洪华山.高血压与炎症关系的研究进展.中国临床药理学与治疗学. 2006, 11:136-140.
19.Ando H, Zhou J, Macova M, Imboden H, Saavedra JM. Angiotensin ii at1 receptor blockade reverses pathological hypertrophy and inflammation in brain microvessels of spontaneously hypertensive rats[J]. Stroke. 2004;35:1726-1731
20. McCarron RM, Wang L, Siren AL, Spatz M, Hallenbeck JM. Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats[J]. Am J Physiol. 1994;267:H2491-2497
21. Spencer CG,Martin Sc,Felmeden Dc,et al.Relationship of homecysteine to msrker8 of platelet and endothelial activation in“high risk”hyportensives:a substudy of the Anglo- andinavian Cardiac Outcomes Trial[J].Int J Cardiol,2004,94(2-3):293-300.
22. Li Li-jun,Yu cheng-Man,Geng Shuren, et al.Endothelial dysfunction in young normotensive subjects with a family history of essential hypertension[J].Xi an MED UNIV,2O02,14(1):81-85.
23. Tham DM, Martin-McNulty B, Wang YX, et al. Angiotensin ii is associated with activation of nf-kappab-mediated genes and downregulation of ppars[J]. Physiol Genomics. 2002;11:21-30
24.何玉辉,刘惠亮.粘附分子与动脉粥样硬化关系的研究进展.疑难病杂志[J].2006,5(2):155-157
25. Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor vii activity in the elderly: Winterinfections and death from cardiovascular disease[J]. Lancet. 1994;343:435-439
26. Topp SA, Upadhya GA, Strasberg SM. Leukocyte adhesion to cold-preserved rat endothelial cells: Role of actin disassembly and icam-1[J]. Liver Transpl. 2003;9:1286-1294
27. Zhang JN, Wood J, Bergeron AL, McBride L, Ball C, Yu Q, Pusiteri AE, Holcomb JB, Dong JF. Effects of low temperature on shear-induced platelet aggregation and activation[J]. J Trauma. 2004;57:216-223
28. Bavendiek U , Libby P , Kilbride M et al . Induction of tissue factor expression in human endothelial cells by CD40 ligand is mediated via activator protein 1 , nuclear factor kappa B and Egr-1[J]. J Biol Chem , 2002 ;277 (28) :25032～9
29. Carnio EC, Branco LG. Participation of the nitric oxide pathway in cold-induced hypertension[J]. Life Sci. 1997;60:1875-1880
30.林健雯,施晓耕,黄如训,等.人工寒潮时不同血压水平大鼠脑卒中发病的实验研究[J].中国神经精神疾病杂志,2005,31(3):180-184.
31.Lawrence T,Gilroy DW,Colville-Nash PR,et al.Possible new role for NF-kappaB in the resolution of inflammation[J].Nat Med,2001,7:1 291
32.Yamamoto K, de Waard V, Fearns C, Loskutoff DJ. Tissue distribution and regulation of murine von willebrand factor gene expression in vivo[J]. Blood. 1998;92:2791-2801
33.Nuotio K, Lindsberg PJ, Carpen O, Soinne L, Lehtonen-Smeds EM, Saimanen E, Lassila R, Sairanen T, Sarna S, Salonen O, Kovanen PT, Kaste M. Adhesion molecule expression in symptomatic and asymptomatic carotid stenosis[J]. Neurology. 2003;60:1890-1899.
1. Falk E , Shah PK, Fuster V. Coronary plaque disruption[J] . Circulation , 1995 , 92 :657.
2.阮长耿.血细胞的粘附分子.中国实验血液学杂志. 2004;12(1):1-5.
3. Ruggeri ZM WJGD. Thrombosis and hemorrhage. Boston: Blackwell Scientific; 1994.
4. Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest. 1973;52:2757-2764.
5. TomJ M,Molenea,Jo apT wisk,et al.P- selectin as a candidate target in atheorsc- lerosis[J] .B i ochemP harm,20 03,66 :859-866
6. Meyer D, Pietu G, Fressinaud E, Girma JP. Von willebrand factor: Structure and function. Mayo Clin Proc. 1991;66:516-523.
7. Simundic AM, Basic V, Topic E, demarin V. et al .Soluble adhesion molecules in acute ischemic stroke. Clin Invest Med. 2004 Apr;27(2):86-92.
8. HubbardA K,R othleinR .In tercellulara dhesionm olecule-1( IC AM-1):expression and cell signaling cascades[J].FereRadioBiol M ed,2000,28(9 ):1379-1386.
9. MathenyH E,D eem TL,Cook-MillsJ M.L ymphocytem igrationt horugh monolayers of endothelial cell lines involves VCAM-1 signaling via endothelial cell NADPH oxi- dase[J]-J Imuno1,2000,164(2):65 50-65 59
11. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999; 340: 115– 126.
12. Barone FC, Feuerstein GZ. Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab. 1999;9:819–834.
13. delZoppo G, Ginis I, Hallenbeck JM, et al. Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathol. 2000;10:95–112.
14. Wang GJ, Deng HY, Maier CM et al. Mild hypothermia reduces ICAM-1 expre- ssion, neutrophil infiltration and microglia /monocyte accumulation followingexperi- mental stroke [ J ]. N euroscience,2002, 114: 1081 - 90.
15. Zaremba J, Losy J. Adhesion molecules of immunoglobulin genesuperfamily in stroke[ J ]. Folia Morphol, 2002, 61 (1) : 1 - 6.
16. Selakovic V, ColicM, JovanovicM et al. Cerebrosp inal fluid and plasma concen- tration of soluble intercellular adhesion molecule 1,vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule in patients with acute ischemic brain disease [ J ].Vojnosanit Pregl, 2003, 60 (2) : 139 - 46.
17. Montaner J, Rovira A, Molina CA et al. Plasmatic level of neuro inflammatory markers p redict the extent of diffusion-weighted image lesions in hyperacute stroke [ J ]. J Cereb B lood Flow M etab,2003, 23 (12) : 1403 - 7.
18. Fardon NJ , Wilkinson R , Thomas TH . Rapid fusion of granules with neutrophil cell membranes in hypertensive patients may increase vascular damage [J ] . A m J Hypertens ,2001 ,14 :927
19. Caimi G,Presti RL ,Carollo C ,et al. Polymorphonuclear integrins ,membrane fluidity , and cytosolic Ca2 + content after activation in essential hypertension[J ] . Hypertension ,2000 ,36 (5) :813
20. Kurose I , Wolf R , Cerwinka W, et al. Microvascular responses to ischemia/ reperfusion in normotensive and hypertensive rats [ J ] .Hypertension ,1999 ,34 (2) :212
21. Elena Galkina; Klaus Ley. Vascular Adhesion Molecules in Atherosclerosis [J].Arterioscler. Thromb. Vasc. Biol. 2007,27: 2292 - 2301.
22.李华,蒲传强,门保忠,等.颈动脉动脉粥样硬化斑块内ICAM-1表达的研究.脑与神经疾病杂志.2005,13:337-339.
23.陈作元.高血压病人细胞黏附分子变化及与危险分级的关系.青岛大学医学院学报.2003,39,78-79.
24. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101:1767-1772.
25. Fassbender K, Bertsch T, Mielke O, Muhlhauser F, Hennerici M. Adhesion molecules in cerebrovascular diseases. Evidence for an inflammatory endothelialactivation in cerebral large- and small-vessel disease. Stroke. 1999;30:1647-1650
26.李敬诚,周华东,张猛,等.脑梗死患者血清可溶性细胞间黏附分子水平变化及其临床意义.中国神经免疫学和神经病学杂志2007 ,14:57-58.
27. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-843
28. Simundic AM, Basic V, Topic E, demarin V. et al .Soluble adhesion molecules in acute ischemic stroke. Clin Invest Med. 2004 Apr;27(2):86-92.
29. Braun M, Pietsch P, Schror K, Baumann G, Felix SB. Cellular adhesion molecules on vascular smooth muscle cells. Cardiovasc Res. 1999;41:395-401
30. Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91:3527-3561
31. Erem C, Hacihasanoglu A, Celik S, Ovali E, Ersoz HO, Ukinc K, Deger O, Telatar M. Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications. Med Princ Pract. 2005;14:22-30
32. Lim HS, Chong AY, Freestone B, Blann AD, Lip GY. The effect of multi-factorial intervention on plasma von willebrand factor, soluble e-selectin and tissue factor in diabetes mellitus: Implications for atherosclerotic vascular disease. Diabet Med. 2005;22:249-255
33. Paramo JA, Beloqui O, Colina I, Diez J, Orbe J. Independent association of von willebrand factor with surrogate markers of atherosclerosis in middle-aged asymptomatic subjects. J Thromb Haemost. 2005;3:662-664
34. Arikan E, Sen S. Endothelial damage and hemostatic markers in patients with uncomplicated mild-to-moderate hypertension and relationship with risk factors. Clin Appl Thromb Hemost. 2005;11:147-159
35.潘剑罡,刘洲.急性脑梗死患者细胞粘附分子- 1、P -选择素和vo n Willebrand因子含量变化及其临床意义研究.神经疾病与精神健康. 2005;5(2):92-94
36. Nurden AT, Bihour C, Macchi L, Lacaze D, Durrieu C, Besse P, Dachary J, Hourdille P. Platelet activation in thrombotic disorders. Nouv Rev Fr Hematol. 1993;35:67-71.
37.楼黎明,杨莉,徐慧连,等.高血压病患者血小板活化状态观察.浙江中西医结合杂志.2006,16:554-556.
38.杜于茜,陈君柱,郑文远,等.高血压颈动脉粥样硬化与P-选择素及C-反应蛋白的关系.临床心血管病杂志.2006,22:180-181.
39. Cihan Ay, Lea V. Jungbauer, Thomas Sailer, et al. High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant. Clinical Chemistry. 2007;53:1235-1243.
40.丁志祥,杨春秀,秦建萍,等.脑梗死患者循环活化血小板的检测及临床意义.国际检验医学杂志.2006,27:104-105.
41. Jean WC, Spellman SR, Nussbaum ES, et al. Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon. Neurosurgery. 1998;43:1382–1396.
42.Bednar MM, Gross CE, Balazy M, et al. Antineutrophil strategies.Neurology. 1997;49(suppl 4):S20–S22.
43. Vemuganti R, Demp sey RJ, Bowen KK. Inhibition of Intercellular adhesion molecule-1 protein expression by antisense oligonucleotides is neuroprotective after transient middle cerebral artery occlusion in rat[ J ]. S troke, 2004, 5 (1) : 179 - 84.
44.向红兵,晋光荣,吴颢昕,等.大鼠多发性脑梗死后脑组织内皮细胞ICAM-1表达的变化.东南大学学报(医学版). 2004,23:295-298.
45.Rosenbers GA.Ischemic brin edema[J].Prog Cardiovasc Dis,1999, 42(3): 209-216.
46.Fujinmura M,Gache Y,Morita Fujimura Y,et al.Early appearance of activated metalloproteinade-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion[J].Brain Res,1999,842(1):92-100.
47. IshikawaM, CooperD, Russell J et al. Molecular determinants of the prothrom- bgenic and inflammatory phenotype assumed by the postischemic cerebral micro-circulation[ J ]. S troke, 2003, 34 ( 7) :1777 - 82.
48.Ritter LS, Orozco JA, Coull BM et al. Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation duringearly reperfusion after stroke[ J ]. Stroke, 2000, 31 (5) : 1153 - 61.
49.Suzuki H ,Abe K, Tojo SJ ,et al . Reduction of ischemic brain injury by anti - P - selectin monoclonal antibody after permanentmiddle cerebral artery occlussion in rat [J ] . Neurol Res ,1999 ,21 :269 - 276.
50.Okada Y,Copeland BR ,Mori E ,et al . P - selectin and intercellular adhesion molecule - 1 expression after focal brain ischemiaand reper - fusion[J ] . St roke ,1994 ,25 :202.
51.D. J. Lefer, D. M. Flynn, D. C. Anderson,et al . Combined inhibition of P-selectin and ICAM-1 reduces myocardial injury following ischemia and reperfusion .Am J Physiol Heart Circ Physiol, 1996, 271: H2421-H2429.
52.Wang X , Feuer shein GZ. Induced expression of adhesion molecules following focal bra - in ischemia [ J ] . Neurot rauma , 1995 ,12 :825 - 832.
53.Haring HP ,Berg EL , Trurusbita N ,et al . E - selectin appears in nonischemic tissue during experimental focal cerebral ischemia[J ] . St roke ,1996 ,27 :1 386 - 1 392..
54.Kozuka K, Kohriyama T ,Nomura E , et al . Endot helial markers and adhesion molecules in acute ischemic st roke sequential changeand differences in stroke sub- type [J ] . At herosclerosis ,2002 ,161 :161 - 168.
55.张世明,孙雪波.鼠脑缺血-再灌注损伤后P、L -选择素表达的研究[J ] .苏州大学学报,2004 ,11 :11 - 14.
56.Rentsch M,PostS,PalmaP,etal.Anti-ICAM-1blockadereducespostsinusoidalWBC adherence following cold ischemia and reperfusion,but does not improve early graft function inratliver transplantation.JHepatol,2000,32(5):821-828.
57.Zhang RL, Zhang ZG, Chopp M, et al. Thrombolysis with tissue plasminogen activator alters adhesion molecule exp ression in the ischemic rat brain[ J ]. Stroke. 1999, 30 (3) : 624～629.
58. Takeda H ,Spatz M ,Ruetzler C ,et al . Induction of mucosal tolerance to E -selectin preve - nt s ischemic and hemorrhagic stroke in spontaneously hypertensive genetically st roke prone rat s [ J ] .St roke ,2002 ,3 319 :2 156 - 2 164.
59. Huang J ,Choudhri TF ,Winf ree CJ ,et al . Post ischemic cerebrovascular E - selectin express - ion mediates tissue injury inmurine stroke[J ] . St roke ,2000 ,31 :3 047 - 3 053.
60. Goussev AV ,Zhang Z ,Andersom DC ,et al . P-selectin antibody reduces hemo- rrhage and i - nfarct volume resulting f rom MCA occlussion in rat [J ] . Nerol Sci ,1998 ,161 :16 - 22.
61. Enlimomab Acute Stroke Trial Investigators. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial[ J ]. Neurology. 2001, 57 (8) : 1428～1434.
62. Furuya K, Takeda H, Azhar S, et al. Examination of several potentialmechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule21antibody: a bedside to bench study [ J ]. Stroke. 2001, 32 ( 11 ) :2665～2674.
63. Luo GX, KohlstaedtLA, Charles CH, et al. Humanization of an anti-ICAM-1 antibody with over 502fold affinity and functional imp rovement[ J ]. J Immunol Methods. 2003, 275 (122) : 31～40.
2.Pan W,Li L,Tsai M.Temperature extremes and mortality from coronary heart disease and cerebral infarction in elderly chinese[J]. Lancet,1995;345: 353-355
3.Hong YC,Rha JH, Lee JT,et al.Ischemic stroke associated with decrease in temperature[J].Epidemiology,2003,14(4):473.
4.黄如训,苏镇培主编.脑卒中[M].人民卫生出版社(北京). 2001年第1版:11.
5.Ronen Sumagin,Ingrid H. A role for ICAM-1 in maintenance of leukocyte- endothelial cell rolling interactions in inflamed arterioles.2007, 293: H2786-H2798
6.Alvaro LC,FreijoMM,Sadaba F.Inflammatory mechanisms, arteriosclerosis and ischemic stroke :clinical data and persperctives [J]. RevNeurol.2002,35:452.
7. Simundic AM, Basic V, Topic E, demarin V. et al .Soluble adhesion molecules in acute ischemic stroke[J]. Clin Invest Med. 2004 Apr;27(2):86-92.
8. Tanne D, Haim M, Boyko V, et al. Soluble intercellular adhesion molecule-1 and risk of future ischemic stroke: A nested case-control study from the bezafibrate infarction prevention (bip) study cohort[J]. Stroke. 2002;33:2182-2186.
9.李敬诚,周华东,张猛,等.脑梗死患者血清可溶性细胞间黏附分子水平变化及其临床意义.中国神经免疫学和神经病学杂志[J].2007 ,14:57-58.
10.Collina T. Biology of disease:Endothelial nuclear factor-κB and initiation of atherosclerotic lesion[J]. Lab Invest ,1993 ;68(5) :499～508.
11.赵峰,室田诚逸,森田育男,等.NF-κB与疾病[J].生命科学,2001, 1(31):11
12.李建军,李庚山. NF-κB与心血管疾病[J].国外医学分子生物学分册, 1999, 21: 123-126
13. Zeng J, Zhang Y, Mo J, Su Z, Huang R. Two-kidney, two clip renovascular hypertensive rats can be used as stroke-prone rats[J]. Stroke. 1998;29:1708-1713; discussion 1713-1704.
14.解龙昌,黄如训,李常新,等.人工寒潮促发脑卒中的实验研究[J].中国神经精神疾病杂志,2004,30(3):198-201.
15.Fardon NJ , Wilkinson R , Thomas TH . Rapid fusion of granules with neutrophil cell membranes in hypertensive patients may increase vascular damage [J] . A m J Hypertension ,2001 ,14 :927
16.Caimi G,Presti RL ,Carollo C ,et al. Polymorphonuclear integrins,membrane fluidity , and cytosolic Ca2+ content after activation in essential hypertension[J] . Hypertension ,2000 ,36 (5) :813
17.Falk E , Shah PK, Fuster V. Coronary plaque disruption[J] . Circulation , 1995 , 92 :657.
18.吴进寿,洪华山.高血压与炎症关系的研究进展.中国临床药理学与治疗学. 2006, 11:136-140.
19.Ando H, Zhou J, Macova M, Imboden H, Saavedra JM. Angiotensin ii at1 receptor blockade reverses pathological hypertrophy and inflammation in brain microvessels of spontaneously hypertensive rats[J]. Stroke. 2004;35:1726-1731
20. McCarron RM, Wang L, Siren AL, Spatz M, Hallenbeck JM. Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats[J]. Am J Physiol. 1994;267:H2491-2497
21. Spencer CG,Martin Sc,Felmeden Dc,et al.Relationship of homecysteine to msrker8 of platelet and endothelial activation in“high risk”hyportensives:a substudy of the Anglo- andinavian Cardiac Outcomes Trial[J].Int J Cardiol,2004,94(2-3):293-300.
22. Li Li-jun,Yu cheng-Man,Geng Shuren, et al.Endothelial dysfunction in young normotensive subjects with a family history of essential hypertension[J].Xi an MED UNIV,2O02,14(1):81-85.
23. Tham DM, Martin-McNulty B, Wang YX, et al. Angiotensin ii is associated with activation of nf-kappab-mediated genes and downregulation of ppars[J]. Physiol Genomics. 2002;11:21-30
24.何玉辉,刘惠亮.粘附分子与动脉粥样硬化关系的研究进展.疑难病杂志[J].2006,5(2):155-157
25. Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor vii activity in the elderly: Winterinfections and death from cardiovascular disease[J]. Lancet. 1994;343:435-439
26. Topp SA, Upadhya GA, Strasberg SM. Leukocyte adhesion to cold-preserved rat endothelial cells: Role of actin disassembly and icam-1[J]. Liver Transpl. 2003;9:1286-1294
27. Zhang JN, Wood J, Bergeron AL, McBride L, Ball C, Yu Q, Pusiteri AE, Holcomb JB, Dong JF. Effects of low temperature on shear-induced platelet aggregation and activation[J]. J Trauma. 2004;57:216-223
28. Bavendiek U , Libby P , Kilbride M et al . Induction of tissue factor expression in human endothelial cells by CD40 ligand is mediated via activator protein 1 , nuclear factor kappa B and Egr-1[J]. J Biol Chem , 2002 ;277 (28) :25032～9
29. Carnio EC, Branco LG. Participation of the nitric oxide pathway in cold-induced hypertension[J]. Life Sci. 1997;60:1875-1880
30.林健雯,施晓耕,黄如训,等.人工寒潮时不同血压水平大鼠脑卒中发病的实验研究[J].中国神经精神疾病杂志,2005,31(3):180-184.
31.Lawrence T,Gilroy DW,Colville-Nash PR,et al.Possible new role for NF-kappaB in the resolution of inflammation[J].Nat Med,2001,7:1 291
32.Yamamoto K, de Waard V, Fearns C, Loskutoff DJ. Tissue distribution and regulation of murine von willebrand factor gene expression in vivo[J]. Blood. 1998;92:2791-2801
33.Nuotio K, Lindsberg PJ, Carpen O, Soinne L, Lehtonen-Smeds EM, Saimanen E, Lassila R, Sairanen T, Sarna S, Salonen O, Kovanen PT, Kaste M. Adhesion molecule expression in symptomatic and asymptomatic carotid stenosis[J]. Neurology. 2003;60:1890-1899.
1. Falk E , Shah PK, Fuster V. Coronary plaque disruption[J] . Circulation , 1995 , 92 :657.
2.阮长耿.血细胞的粘附分子.中国实验血液学杂志. 2004;12(1):1-5.
3. Ruggeri ZM WJGD. Thrombosis and hemorrhage. Boston: Blackwell Scientific; 1994.
4. Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest. 1973;52:2757-2764.
5. TomJ M,Molenea,Jo apT wisk,et al.P- selectin as a candidate target in atheorsc- lerosis[J] .B i ochemP harm,20 03,66 :859-866
6. Meyer D, Pietu G, Fressinaud E, Girma JP. Von willebrand factor: Structure and function. Mayo Clin Proc. 1991;66:516-523.
7. Simundic AM, Basic V, Topic E, demarin V. et al .Soluble adhesion molecules in acute ischemic stroke. Clin Invest Med. 2004 Apr;27(2):86-92.
8. HubbardA K,R othleinR .In tercellulara dhesionm olecule-1( IC AM-1):expression and cell signaling cascades[J].FereRadioBiol M ed,2000,28(9 ):1379-1386.
9. MathenyH E,D eem TL,Cook-MillsJ M.L ymphocytem igrationt horugh monolayers of endothelial cell lines involves VCAM-1 signaling via endothelial cell NADPH oxi- dase[J]-J Imuno1,2000,164(2):65 50-65 59
11. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999; 340: 115– 126.
12. Barone FC, Feuerstein GZ. Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab. 1999;9:819–834.
13. delZoppo G, Ginis I, Hallenbeck JM, et al. Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathol. 2000;10:95–112.
14. Wang GJ, Deng HY, Maier CM et al. Mild hypothermia reduces ICAM-1 expre- ssion, neutrophil infiltration and microglia /monocyte accumulation followingexperi- mental stroke [ J ]. N euroscience,2002, 114: 1081 - 90.
15. Zaremba J, Losy J. Adhesion molecules of immunoglobulin genesuperfamily in stroke[ J ]. Folia Morphol, 2002, 61 (1) : 1 - 6.
16. Selakovic V, ColicM, JovanovicM et al. Cerebrosp inal fluid and plasma concen- tration of soluble intercellular adhesion molecule 1,vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule in patients with acute ischemic brain disease [ J ].Vojnosanit Pregl, 2003, 60 (2) : 139 - 46.
17. Montaner J, Rovira A, Molina CA et al. Plasmatic level of neuro inflammatory markers p redict the extent of diffusion-weighted image lesions in hyperacute stroke [ J ]. J Cereb B lood Flow M etab,2003, 23 (12) : 1403 - 7.
18. Fardon NJ , Wilkinson R , Thomas TH . Rapid fusion of granules with neutrophil cell membranes in hypertensive patients may increase vascular damage [J ] . A m J Hypertens ,2001 ,14 :927
19. Caimi G,Presti RL ,Carollo C ,et al. Polymorphonuclear integrins ,membrane fluidity , and cytosolic Ca2 + content after activation in essential hypertension[J ] . Hypertension ,2000 ,36 (5) :813
20. Kurose I , Wolf R , Cerwinka W, et al. Microvascular responses to ischemia/ reperfusion in normotensive and hypertensive rats [ J ] .Hypertension ,1999 ,34 (2) :212
21. Elena Galkina; Klaus Ley. Vascular Adhesion Molecules in Atherosclerosis [J].Arterioscler. Thromb. Vasc. Biol. 2007,27: 2292 - 2301.
22.李华,蒲传强,门保忠,等.颈动脉动脉粥样硬化斑块内ICAM-1表达的研究.脑与神经疾病杂志.2005,13:337-339.
23.陈作元.高血压病人细胞黏附分子变化及与危险分级的关系.青岛大学医学院学报.2003,39,78-79.
24. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101:1767-1772.
25. Fassbender K, Bertsch T, Mielke O, Muhlhauser F, Hennerici M. Adhesion molecules in cerebrovascular diseases. Evidence for an inflammatory endothelialactivation in cerebral large- and small-vessel disease. Stroke. 1999;30:1647-1650
26.李敬诚,周华东,张猛,等.脑梗死患者血清可溶性细胞间黏附分子水平变化及其临床意义.中国神经免疫学和神经病学杂志2007 ,14:57-58.
27. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-843
28. Simundic AM, Basic V, Topic E, demarin V. et al .Soluble adhesion molecules in acute ischemic stroke. Clin Invest Med. 2004 Apr;27(2):86-92.
29. Braun M, Pietsch P, Schror K, Baumann G, Felix SB. Cellular adhesion molecules on vascular smooth muscle cells. Cardiovasc Res. 1999;41:395-401
30. Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91:3527-3561
31. Erem C, Hacihasanoglu A, Celik S, Ovali E, Ersoz HO, Ukinc K, Deger O, Telatar M. Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications. Med Princ Pract. 2005;14:22-30
32. Lim HS, Chong AY, Freestone B, Blann AD, Lip GY. The effect of multi-factorial intervention on plasma von willebrand factor, soluble e-selectin and tissue factor in diabetes mellitus: Implications for atherosclerotic vascular disease. Diabet Med. 2005;22:249-255
33. Paramo JA, Beloqui O, Colina I, Diez J, Orbe J. Independent association of von willebrand factor with surrogate markers of atherosclerosis in middle-aged asymptomatic subjects. J Thromb Haemost. 2005;3:662-664
34. Arikan E, Sen S. Endothelial damage and hemostatic markers in patients with uncomplicated mild-to-moderate hypertension and relationship with risk factors. Clin Appl Thromb Hemost. 2005;11:147-159
35.潘剑罡,刘洲.急性脑梗死患者细胞粘附分子- 1、P -选择素和vo n Willebrand因子含量变化及其临床意义研究.神经疾病与精神健康. 2005;5(2):92-94
36. Nurden AT, Bihour C, Macchi L, Lacaze D, Durrieu C, Besse P, Dachary J, Hourdille P. Platelet activation in thrombotic disorders. Nouv Rev Fr Hematol. 1993;35:67-71.
37.楼黎明,杨莉,徐慧连,等.高血压病患者血小板活化状态观察.浙江中西医结合杂志.2006,16:554-556.
38.杜于茜,陈君柱,郑文远,等.高血压颈动脉粥样硬化与P-选择素及C-反应蛋白的关系.临床心血管病杂志.2006,22:180-181.
39. Cihan Ay, Lea V. Jungbauer, Thomas Sailer, et al. High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant. Clinical Chemistry. 2007;53:1235-1243.
40.丁志祥,杨春秀,秦建萍,等.脑梗死患者循环活化血小板的检测及临床意义.国际检验医学杂志.2006,27:104-105.
41. Jean WC, Spellman SR, Nussbaum ES, et al. Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon. Neurosurgery. 1998;43:1382–1396.
42.Bednar MM, Gross CE, Balazy M, et al. Antineutrophil strategies.Neurology. 1997;49(suppl 4):S20–S22.
43. Vemuganti R, Demp sey RJ, Bowen KK. Inhibition of Intercellular adhesion molecule-1 protein expression by antisense oligonucleotides is neuroprotective after transient middle cerebral artery occlusion in rat[ J ]. S troke, 2004, 5 (1) : 179 - 84.
44.向红兵,晋光荣,吴颢昕,等.大鼠多发性脑梗死后脑组织内皮细胞ICAM-1表达的变化.东南大学学报(医学版). 2004,23:295-298.
45.Rosenbers GA.Ischemic brin edema[J].Prog Cardiovasc Dis,1999, 42(3): 209-216.
46.Fujinmura M,Gache Y,Morita Fujimura Y,et al.Early appearance of activated metalloproteinade-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion[J].Brain Res,1999,842(1):92-100.
47. IshikawaM, CooperD, Russell J et al. Molecular determinants of the prothrom- bgenic and inflammatory phenotype assumed by the postischemic cerebral micro-circulation[ J ]. S troke, 2003, 34 ( 7) :1777 - 82.
48.Ritter LS, Orozco JA, Coull BM et al. Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation duringearly reperfusion after stroke[ J ]. Stroke, 2000, 31 (5) : 1153 - 61.
49.Suzuki H ,Abe K, Tojo SJ ,et al . Reduction of ischemic brain injury by anti - P - selectin monoclonal antibody after permanentmiddle cerebral artery occlussion in rat [J ] . Neurol Res ,1999 ,21 :269 - 276.
50.Okada Y,Copeland BR ,Mori E ,et al . P - selectin and intercellular adhesion molecule - 1 expression after focal brain ischemiaand reper - fusion[J ] . St roke ,1994 ,25 :202.
51.D. J. Lefer, D. M. Flynn, D. C. Anderson,et al . Combined inhibition of P-selectin and ICAM-1 reduces myocardial injury following ischemia and reperfusion .Am J Physiol Heart Circ Physiol, 1996, 271: H2421-H2429.
52.Wang X , Feuer shein GZ. Induced expression of adhesion molecules following focal bra - in ischemia [ J ] . Neurot rauma , 1995 ,12 :825 - 832.
53.Haring HP ,Berg EL , Trurusbita N ,et al . E - selectin appears in nonischemic tissue during experimental focal cerebral ischemia[J ] . St roke ,1996 ,27 :1 386 - 1 392..
54.Kozuka K, Kohriyama T ,Nomura E , et al . Endot helial markers and adhesion molecules in acute ischemic st roke sequential changeand differences in stroke sub- type [J ] . At herosclerosis ,2002 ,161 :161 - 168.
55.张世明,孙雪波.鼠脑缺血-再灌注损伤后P、L -选择素表达的研究[J ] .苏州大学学报,2004 ,11 :11 - 14.
56.Rentsch M,PostS,PalmaP,etal.Anti-ICAM-1blockadereducespostsinusoidalWBC adherence following cold ischemia and reperfusion,but does not improve early graft function inratliver transplantation.JHepatol,2000,32(5):821-828.
57.Zhang RL, Zhang ZG, Chopp M, et al. Thrombolysis with tissue plasminogen activator alters adhesion molecule exp ression in the ischemic rat brain[ J ]. Stroke. 1999, 30 (3) : 624～629.
58. Takeda H ,Spatz M ,Ruetzler C ,et al . Induction of mucosal tolerance to E -selectin preve - nt s ischemic and hemorrhagic stroke in spontaneously hypertensive genetically st roke prone rat s [ J ] .St roke ,2002 ,3 319 :2 156 - 2 164.
59. Huang J ,Choudhri TF ,Winf ree CJ ,et al . Post ischemic cerebrovascular E - selectin express - ion mediates tissue injury inmurine stroke[J ] . St roke ,2000 ,31 :3 047 - 3 053.
60. Goussev AV ,Zhang Z ,Andersom DC ,et al . P-selectin antibody reduces hemo- rrhage and i - nfarct volume resulting f rom MCA occlussion in rat [J ] . Nerol Sci ,1998 ,161 :16 - 22.
61. Enlimomab Acute Stroke Trial Investigators. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial[ J ]. Neurology. 2001, 57 (8) : 1428～1434.
62. Furuya K, Takeda H, Azhar S, et al. Examination of several potentialmechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule21antibody: a bedside to bench study [ J ]. Stroke. 2001, 32 ( 11 ) :2665～2674.
63. Luo GX, KohlstaedtLA, Charles CH, et al. Humanization of an anti-ICAM-1 antibody with over 502fold affinity and functional imp rovement[ J ]. J Immunol Methods. 2003, 275 (122) : 31～40.