血栓烷与血管性痴呆的关系的研究
摘要
目的 阿司匹林(aspirin, acetylsalicylic acid, ASA)广泛应用于血管性痴呆(vascular dementia, VD)的患者，有几个研究已提出了ASA可能对痴呆的发生和进展及一般所说的认知功能有好的作用。因此我们研究了血栓烷A_2(thromboxane A_2)的合成(表现为血浆中血栓烷B_2的水平)与血管性痴呆的关系。方法 应用放射免疫分析的方法，检测了34例血管性痴呆患者、30例卒中后非痴呆患者及27例健康人血中的TXB_2水平。结果 血管性痴呆组TXB_2值为109.21±48.65pg／ml；卒中后非痴呆组TXB_2值为86.64±33.45pg／ml；正常对照者TXB_2值为70.03±12.95pg／ml。血管性痴呆组TXB_2值高于卒中后非痴呆组，有显著性差异(P＜0.05)；而且血管性痴呆组和卒中后非痴呆组TXB_2值均高于正常对照组，P＜0.05。卒中后不用ASA组TXB_2值为112.77±47.03pg／ml；卒中后服用ASA组TXB_2值为87.63±37.42pg／ml。卒中后不用ASA组比卒中后服用ASA组TXB_2值高，P＜0.05；而且，两组均比正常对照组TXB_2值高，P＜0.05。结论 血管性痴呆组较卒中后非痴呆组TXB_2水平增高，血浆中血栓烷水平与血管性痴呆有关，血管性痴呆患者可能有一重要的对ASA不敏感的血栓烷合成。其机制尚待进一步研究。
Objective Aspirin (acetylsalicylic acid, ASA) is widely prescribed for patients with a diagnosis of vascular dementia(VD). It has been suggested that daily intake of aspirin is associated with a reduction of cognitive decline, both in normal and in demented subjects, but the mechanism is unclear. We have therefore studied thromboxane (TX) A2 biosynthesis, as reflected by the level of TXB2, in vascular dementia (VD) patients to ascertain if the thromboxane B2 ( TXB2 ) is associated with vascular dementia ( VD ) . Methods The radioimmunoassay was used to detect TXB2 in 34 VD patients, 30 patients who was not demented after stroke, and 27 healthy age-matched controls. Results Mean value of TXB2was 109. 21 + 48. 65pg/ml for VD patients; 86.64±33. 45pg/ml for the patients who was not demented after stroke (P<0. 05); and 70.03 ± 12. 95pg/ml for the healthy controls. The level of TXB2 was higher in VD than that in the patients who was not demented after stroke (P<0. 05); and both of that were higher than that in th
e healthy controls (P<0.05). Mean value of TXB2was 112. 77±47. 03pg/ml for the patients who did not use acetylsalicylic acid (ASA) after stroke versus 87. 63+37. 42pg/ml for the patients who used ASA., and the former was significantly higher than the latter (P<0.05); furthermore, both of that were higher than that in healthy controls (P<0. 05). Conclusions TXB2 was increased in vascular dementia patients than that in patients who was not demented after stroke . TXB2 is associated with vascular dementia. VD patients may have an important aspirin-insensitive source of
thromboxane biosynthesis. The mechanism is unclear.
Tian Van (Neurology) Directed by Tan Lan
Objective Aspirin (acetylsalicylic acid, ASA) is widely prescribed for patients with a diagnosis of vascular dementia(VD). It has been suggested that daily intake of aspirin is associated with a reduction of cognitive decline, both in normal and in demented subjects, but the mechanism is unclear. We have therefore studied thromboxane (TX) A2 biosynthesis, as reflected by the level of TXB2, in vascular dementia (VD) patients to ascertain if the thromboxane B2 ( TXB2 ) is associated with vascular dementia ( VD ) . Methods The radioimmunoassay was used to detect TXB2 in 34 VD patients, 30 patients who was not demented after stroke, and 27 healthy age-matched controls. Results Mean value of TXB2was 109. 21 + 48. 65pg/ml for VD patients; 86.64±33. 45pg/ml for the patients who was not demented after stroke (P<0. 05); and 70.03 ± 12. 95pg/ml for the healthy controls. The level of TXB2 was higher in VD than that in the patients who was not demented after stroke (P<0. 05); and both of that were higher than that in th
e healthy controls (P<0.05). Mean value of TXB2was 112. 77±47. 03pg/ml for the patients who did not use acetylsalicylic acid (ASA) after stroke versus 87. 63+37. 42pg/ml for the patients who used ASA., and the former was significantly higher than the latter (P<0.05); furthermore, both of that were higher than that in healthy controls (P<0. 05). Conclusions TXB2 was increased in vascular dementia patients than that in patients who was not demented after stroke . TXB2 is associated with vascular dementia. VD patients may have an important aspirin-insensitive source of
thromboxane biosynthesis. The mechanism is unclear.
Tian Van (Neurology) Directed by Tan Lan
引文
1 Desmond DW, BagiellaE, Moroney JT, et al. The effect of patient attrition on estimates of the frequency of dementia following stroke. Arch Neurology 1998; 55:390-4
2 Kokmen E, Whisnant JP, O' Fallen WM, et al. Dementia after ischaemic stroke: a population-based study in Rochester, Minnesota 1960-1984． Neurol 1996; 46:154-9
3 Phillips NA, Mate-Kole CC. Cognitive deficits in peripheral vascular disease. A comparison of mild stroke patients and normal control subjects. Stroke 1997; 28:777-84
4 Loeb C, Gandolfo C, Croce R, et al. Dementia associated with lacunar infarction. Stroke 1992; 23:1225-1229
5 Tatemichi TK, Desmond DW, Mayeux R, et al. Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort. Neurology 1992; 42:1185-1193
6 Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994:330:1287-1294
7 Brash AR. Arachidonic acid as a bioactive molecule. J. Clin. Invest. 2001,107:1339-1345
8 Sugimoto Y, Narurmiya S, Ichikawa A. Distribution and function of prostanoid receptors: studies from knockout mice. Prog. Lipid Res. 2000,39:289-314
9 Patrignani P, et al. Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J. Pharmacol. Exp. Ther. 1994,271:1705-1712
10 Stenberg PE, Mcerer RP, Shumam Ma, et al. A platelet alpha-granule
membraneprotion(GMP-140) is expressed on the plasma after activation.J cell Bio1,1995,101:880
11 叶和军，林求诚。原发性高血压患者血小板内游离Ca~(2+)浓度与血浆TxA2一PG I2平衡系统的关系。临床心血管病杂志 2000，16(1)，23-24
12 朱伟，许文荣，焦志军等。血浆PAF、TXB_2和6-k-PGF_(1a)检测在老年脑梗塞、高血压患者中的临床意义。临床检验杂志1998，16(4)223-226
13 王中。高血压病患者血小板活化状态研究。河北医药 2002，24(9)：713-714
14 胡翊群，丁磊，陈扑。11—去氢—血栓烷B：和11—β—前列腺素F(2a)在糖尿病病人中变化的初探。诊断学理论与实践2002，1(1)：41-44
15 付正菊，刘竹珍，于宏伟。糖尿病患者血管病变与血小板活化功能状态的关系。山东医药 1998，38(11)：6-7
16 东平，杨裕国，吴万龄。糖尿病患者血小板活化状态和纤溶活性的变化。实用医学杂志 1999，15(6)：425-426
17 张明雪。血小板与冠心病发病机理研究概况。辽宁中医学院学报 2002，4(1)：67-68
18 赵一，吴高鹏。老年人血脂水平对血小板活化释放状态影响的研究。上海医学检验杂志 2001，16(4)：206-208
19 冯莹，王兆钺。冠心病和PTCA前后11—去氢—血栓烷B2的测定及临床意义。新医学。1997，28(增刊)：8-9
20 van Kooten F, Ciabattoni G, Patrono C, et al. Evidence for episodic platelet activation in acute ischemic stroke. Stroke. 1994;25(2):278-81
21 常红、崔永等。缺血性脑血管病TXB2、PGl2的追踪观察。中国厂矿医学。2001；14(6)：444-445
22 van Kooten F, Ciabattoni G, Patrono C, et al. Increased platelet activation in the chronic phase after cerebral ischemia and interacerebral hemorrhage. Stroke. 1999:30:546-549
23 李廷谦等。肺心病患者血浆TXB_2和6-keto-PGF_(2a)含量的动态观察。华西医科大学学报。1996；27(3)：320—322
24 白晓玲，郭卫民，段晓辉，等。血小板活化状态与原发性肾病综合征患儿高凝状态的研究。肾脏病与透析肾移植杂志，1999，8：34-35
25 刘高金。原发性肾病综合征患儿血浆11—去氢—血栓烷B_2的测定及临床意义。江苏医药杂志 2002：28(8)：607-609
26 李红叶、王华等。小儿原发性肾病综合征患者血凝状态测定。河南医科大学学报 2001；36(1)：58-60
27 卢国元，李声宏，朱玉芳等。系统性红斑狼疮患者血浆11—去氢血栓烷B_2测定及其临床意义。中华风湿病学杂志 2001，5(3)：165-167
28 Ferro D, Basili S, Roccaforte S, et al. Determinants of enhanced thromboxane giosynthesis in patients with systemic erythematosus。Arthritis Rheum. 1999,42:2869
29 van Kooten F, Ciabattoni G, Patrono C, et al. Platelet activetion and lipid peroxidation in patient with acute ischemic stroke. Stroke. 1997;28:1557-1563
30 汤钊猷主编。现代肿瘤学。上海：上海医科大学出版社．1993，104
31 陈令松、王少青。恶性肿瘤患者血中TXB_2和6—KP的临床意义。徐州医学院学报 1999，19(4)：298-299
32 Majerus PW. Arachidonate metabolism in vascular disorders. J Clin Invest 1983; 72:1521-1525
33 Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and-2. J Biol Chem 1996; 271:33157-33160
34 Loll PJ, Picot D, 6aravito RM. The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. Nat Struct Biol 1995; 2:637-643
35 Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest 1982:69:1366-1372
36 Braden GA, Knapp HR, FitzGerald GA. Suppression of eicosanoid biosynthesis during coronary angioplasty by fish oil and aspirin. Circulation 1991:84:679-685
37 Catella-Lawson F, McAdam B, Morrison BW, et al. Effects of selective inhibition of cyclooxygenase II on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 1999; 289:735-741
38 McAdam BF, Catella-Lawson F, Mardini I, et al. Systemic biosynthesis of prostacyclin by cyclooxygenase(COX)-2:the humen pharmacology of a selective inhibitor of COX-2． Proc Natl Acad Sci USA 1999:96:272-277
39 Cullen L, Kelly L, Connor SO, et al. Selective cyclooxygenase-2 inhibition by nimesulide in man. J Pharmacol Exp Ther 1998:287:578-582
40 Helgason CM, Hoff JA, Kondos GT, et al . Platelet aggregation in patients with atrial fibrillation taking aspirin or warfarin. Stroke 1993:24:1458-1461
41 Helgason CM, Tortorice KL, Winkler SR, et al . Aspirin response and failure in cerebral infarction. Stroke 1993:24:345-350
42 Helgason CM, Bolin KM, Hoff JA, et al . Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994:25:2331-2336
43 Buchanan MR, Brister SJ . Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol 1995:11:221-227
44 Meyer JS, Rogers RL, McClintic K, et al. Randomized Clinical Trial of Daily Aspirin Therapy in Multi-Infarct Dementia, A Pilot Study. J AM Geriatr Soc
1989 Jun; 37(6) :549-55
45 Sturmer T, Glynn RJ, Field TS, et al. Aspirin Use and Cognitive Function in the Elderly. AM J Epidemiol 1996; 143(7) :683-91
46 Richards M, Meade TW, Peart S, et al. Is there any evidence for a protective effect of antithrombotic medication on cognitive function in men at risk of cardiovascular disease? Some preliminary findings. J Neurol Neurosurg Psychiatry 1997 Mar;62(3) :269-72
47 Peacock JM, Folsom AR, Knopman DS, et al. Association of nonsteroidal anti-inflammatory drugs and aspirin with cognitive performance in middle-aged adults. Neuroepidemiology 1999;18(3) :134-43
48 Austermann M, Grotemeyer KH, Evers S, et al. The influence of acetylsalicylic acid on cognitive processing: an event-related potentials study. Psychopharmacology(Berl) 1998 Aug;138(3-4) :369-74
49 May FE, Moore MT, Stewart RB, et al. Lack of association of nonsteroidal anti-inflammatory drug use and cognitive decline in the elderly. Gerontology 1992;38(5) :275-9
50 Henderson AS, Jorm AF, Christensen H, et al. Aspirin, Anti-inflammatory drugs and risk of dementia. International Journal of Geriatric Psychiatry 1997:12:926-30
51 Breitner JC, Gau BA, Welsh KA, et al. Inverse association of anti-inflammatory treatments and Alzheimer' s disease:Initial results of a co-twin control study. Neurology, 1994, 44(3) :227-232
52 De Reuck J, Decoo D, Marchau M, et al. Positron emission tomography in vascular dementia. J Neurol Sci, 1998;154:55-61．
53 Chemtob S, Beharry K, Barna T, et al. Differences in the effects of newborn piglet of various non-steroidal anti-inflammatory drugs on cerebral blood
flow but not on cerebrovascular prostaglandins. Pediatr Res 1991:30:106-111
54 Kuhn W, Muller T, Buttner T, et al. Aspirin as a free radical scavenger:consequences for therapy of cerebrovascular ischemia. Stroke,1995, 26(10) :1959-1960
55 Oberle S, Polte T, Abate A, et al. Aspirin increase Feoritin synthesis in Endothelial cells, A Novel antioxidant pathway. Circ Res, 1998, 82(9) :1016-1020
56 Daya S, Walker RB, Anoopkumar-Dukie S. Cyanide-induced free radical production and lipid peroxidation in rat brain homogenate is reduced by Aspirin. Metab Brain Dis, 2000, 15(3) :203-210
57 Asanuma M, Nishibayashi-Asanma S, Miyazaki I, et al. Neuroprotective effects of non-steroidal anti-inflammatory drug by direct scavenging of Nitric oxide radicals. J Neurochem, 2001, 76(6) 1895-1904
58 Riepe MW, Kasischke K, Raupach A. Acetylsalicylic Acid increases tolerance against hypoxic and chemical hypoxia. Stroke, 1997, 28(10) :2006-2011
59 Moro MA, De-alba J, Cardenas A, et al. Mechanisms of the neuroprotective effect of aspirin after oxygen and glucose deprivation in rat forebrain slices. Neuropharmacology, 2000, 39(7) :1309-1318
60 Lee YJ, Jy W, Horstman LL, et al. Elevated platelet microparticles in transient ischemic attacks, lacunar infarcts, and multiinfarct dementias. Thromb Res 1993;72(4) :295-304
61 van Kooten F, Ciabattoni G, Patrono C, et al. Increased thromboxane biosynthesis is associated with poststroke dementia. Stroke. 1999:30:1542-1547
62 Davi G, Gresele P, Violi F, et al. Diabetes mellitus, hypercholesterolemia,
and hypertension but not vascular disease perse are associated with persistent platelet activation in vivo: evidence derived from the study of peripheral arterial disease. Circulation. 1997:96:69-75
63 Eikelboom JW, Hirsh J, Weitz JI, et al. Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events. Circulation. 2002:105:1650
2 Kokmen E, Whisnant JP, O' Fallen WM, et al. Dementia after ischaemic stroke: a population-based study in Rochester, Minnesota 1960-1984． Neurol 1996; 46:154-9
3 Phillips NA, Mate-Kole CC. Cognitive deficits in peripheral vascular disease. A comparison of mild stroke patients and normal control subjects. Stroke 1997; 28:777-84
4 Loeb C, Gandolfo C, Croce R, et al. Dementia associated with lacunar infarction. Stroke 1992; 23:1225-1229
5 Tatemichi TK, Desmond DW, Mayeux R, et al. Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort. Neurology 1992; 42:1185-1193
6 Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994:330:1287-1294
7 Brash AR. Arachidonic acid as a bioactive molecule. J. Clin. Invest. 2001,107:1339-1345
8 Sugimoto Y, Narurmiya S, Ichikawa A. Distribution and function of prostanoid receptors: studies from knockout mice. Prog. Lipid Res. 2000,39:289-314
9 Patrignani P, et al. Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J. Pharmacol. Exp. Ther. 1994,271:1705-1712
10 Stenberg PE, Mcerer RP, Shumam Ma, et al. A platelet alpha-granule
membraneprotion(GMP-140) is expressed on the plasma after activation.J cell Bio1,1995,101:880
11 叶和军，林求诚。原发性高血压患者血小板内游离Ca~(2+)浓度与血浆TxA2一PG I2平衡系统的关系。临床心血管病杂志 2000，16(1)，23-24
12 朱伟，许文荣，焦志军等。血浆PAF、TXB_2和6-k-PGF_(1a)检测在老年脑梗塞、高血压患者中的临床意义。临床检验杂志1998，16(4)223-226
13 王中。高血压病患者血小板活化状态研究。河北医药 2002，24(9)：713-714
14 胡翊群，丁磊，陈扑。11—去氢—血栓烷B：和11—β—前列腺素F(2a)在糖尿病病人中变化的初探。诊断学理论与实践2002，1(1)：41-44
15 付正菊，刘竹珍，于宏伟。糖尿病患者血管病变与血小板活化功能状态的关系。山东医药 1998，38(11)：6-7
16 东平，杨裕国，吴万龄。糖尿病患者血小板活化状态和纤溶活性的变化。实用医学杂志 1999，15(6)：425-426
17 张明雪。血小板与冠心病发病机理研究概况。辽宁中医学院学报 2002，4(1)：67-68
18 赵一，吴高鹏。老年人血脂水平对血小板活化释放状态影响的研究。上海医学检验杂志 2001，16(4)：206-208
19 冯莹，王兆钺。冠心病和PTCA前后11—去氢—血栓烷B2的测定及临床意义。新医学。1997，28(增刊)：8-9
20 van Kooten F, Ciabattoni G, Patrono C, et al. Evidence for episodic platelet activation in acute ischemic stroke. Stroke. 1994;25(2):278-81
21 常红、崔永等。缺血性脑血管病TXB2、PGl2的追踪观察。中国厂矿医学。2001；14(6)：444-445
22 van Kooten F, Ciabattoni G, Patrono C, et al. Increased platelet activation in the chronic phase after cerebral ischemia and interacerebral hemorrhage. Stroke. 1999:30:546-549
23 李廷谦等。肺心病患者血浆TXB_2和6-keto-PGF_(2a)含量的动态观察。华西医科大学学报。1996；27(3)：320—322
24 白晓玲，郭卫民，段晓辉，等。血小板活化状态与原发性肾病综合征患儿高凝状态的研究。肾脏病与透析肾移植杂志，1999，8：34-35
25 刘高金。原发性肾病综合征患儿血浆11—去氢—血栓烷B_2的测定及临床意义。江苏医药杂志 2002：28(8)：607-609
26 李红叶、王华等。小儿原发性肾病综合征患者血凝状态测定。河南医科大学学报 2001；36(1)：58-60
27 卢国元，李声宏，朱玉芳等。系统性红斑狼疮患者血浆11—去氢血栓烷B_2测定及其临床意义。中华风湿病学杂志 2001，5(3)：165-167
28 Ferro D, Basili S, Roccaforte S, et al. Determinants of enhanced thromboxane giosynthesis in patients with systemic erythematosus。Arthritis Rheum. 1999,42:2869
29 van Kooten F, Ciabattoni G, Patrono C, et al. Platelet activetion and lipid peroxidation in patient with acute ischemic stroke. Stroke. 1997;28:1557-1563
30 汤钊猷主编。现代肿瘤学。上海：上海医科大学出版社．1993，104
31 陈令松、王少青。恶性肿瘤患者血中TXB_2和6—KP的临床意义。徐州医学院学报 1999，19(4)：298-299
32 Majerus PW. Arachidonate metabolism in vascular disorders. J Clin Invest 1983; 72:1521-1525
33 Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and-2. J Biol Chem 1996; 271:33157-33160
34 Loll PJ, Picot D, 6aravito RM. The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. Nat Struct Biol 1995; 2:637-643
35 Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest 1982:69:1366-1372
36 Braden GA, Knapp HR, FitzGerald GA. Suppression of eicosanoid biosynthesis during coronary angioplasty by fish oil and aspirin. Circulation 1991:84:679-685
37 Catella-Lawson F, McAdam B, Morrison BW, et al. Effects of selective inhibition of cyclooxygenase II on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 1999; 289:735-741
38 McAdam BF, Catella-Lawson F, Mardini I, et al. Systemic biosynthesis of prostacyclin by cyclooxygenase(COX)-2:the humen pharmacology of a selective inhibitor of COX-2． Proc Natl Acad Sci USA 1999:96:272-277
39 Cullen L, Kelly L, Connor SO, et al. Selective cyclooxygenase-2 inhibition by nimesulide in man. J Pharmacol Exp Ther 1998:287:578-582
40 Helgason CM, Hoff JA, Kondos GT, et al . Platelet aggregation in patients with atrial fibrillation taking aspirin or warfarin. Stroke 1993:24:1458-1461
41 Helgason CM, Tortorice KL, Winkler SR, et al . Aspirin response and failure in cerebral infarction. Stroke 1993:24:345-350
42 Helgason CM, Bolin KM, Hoff JA, et al . Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994:25:2331-2336
43 Buchanan MR, Brister SJ . Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol 1995:11:221-227
44 Meyer JS, Rogers RL, McClintic K, et al. Randomized Clinical Trial of Daily Aspirin Therapy in Multi-Infarct Dementia, A Pilot Study. J AM Geriatr Soc
1989 Jun; 37(6) :549-55
45 Sturmer T, Glynn RJ, Field TS, et al. Aspirin Use and Cognitive Function in the Elderly. AM J Epidemiol 1996; 143(7) :683-91
46 Richards M, Meade TW, Peart S, et al. Is there any evidence for a protective effect of antithrombotic medication on cognitive function in men at risk of cardiovascular disease? Some preliminary findings. J Neurol Neurosurg Psychiatry 1997 Mar;62(3) :269-72
47 Peacock JM, Folsom AR, Knopman DS, et al. Association of nonsteroidal anti-inflammatory drugs and aspirin with cognitive performance in middle-aged adults. Neuroepidemiology 1999;18(3) :134-43
48 Austermann M, Grotemeyer KH, Evers S, et al. The influence of acetylsalicylic acid on cognitive processing: an event-related potentials study. Psychopharmacology(Berl) 1998 Aug;138(3-4) :369-74
49 May FE, Moore MT, Stewart RB, et al. Lack of association of nonsteroidal anti-inflammatory drug use and cognitive decline in the elderly. Gerontology 1992;38(5) :275-9
50 Henderson AS, Jorm AF, Christensen H, et al. Aspirin, Anti-inflammatory drugs and risk of dementia. International Journal of Geriatric Psychiatry 1997:12:926-30
51 Breitner JC, Gau BA, Welsh KA, et al. Inverse association of anti-inflammatory treatments and Alzheimer' s disease:Initial results of a co-twin control study. Neurology, 1994, 44(3) :227-232
52 De Reuck J, Decoo D, Marchau M, et al. Positron emission tomography in vascular dementia. J Neurol Sci, 1998;154:55-61．
53 Chemtob S, Beharry K, Barna T, et al. Differences in the effects of newborn piglet of various non-steroidal anti-inflammatory drugs on cerebral blood
flow but not on cerebrovascular prostaglandins. Pediatr Res 1991:30:106-111
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