• 四川大學(xué)華西醫(yī)院神經(jīng)內(nèi)科（成都 610041 ）;

目的 　了解血漿基質(zhì)金屬蛋白酶-9（matrix metalloproteinase-9, MMP-9）與缺血性卒中出血轉(zhuǎn)化的關(guān)系，以便為患者選擇恰當(dāng)?shù)娜芩ㄖ委熀团R床應(yīng)用基質(zhì)金屬蛋白酶抑制劑，擴(kuò)大溶栓治療時(shí)間窗以及進(jìn)一步臨床研究提供參考依據(jù)。
方法 　納入血漿MMP-9與缺血性卒中出血轉(zhuǎn)化關(guān)系的臨床研究，根據(jù)血漿MMP-9水平是否高于界值、隨訪發(fā)生出血轉(zhuǎn)化的情況，或者根據(jù)是否有出血轉(zhuǎn)化比較血漿MMP-9水平的臨床研究，發(fā)表語種不限。按照缺血性腦血管病、MMP-9和出血轉(zhuǎn)化的同義詞和不同的拼寫形式組成檢索式分別在MEDLINE（1966～2006.4）和EMBASE（1966～2006.4）以及漢語檢索工具CNKI（1977～2006.2）和萬方數(shù)據(jù)庫（1989～2005）檢索，并根據(jù)選出文章的參考文獻(xiàn)目錄追蹤檢索。根據(jù)研究類型，按照預(yù)后研究方法學(xué)評價(jià)的主要標(biāo)準(zhǔn)，由兩位研究者獨(dú)立評價(jià)研究質(zhì)量，意見不一致時(shí)請第三方協(xié)助評價(jià)。提取出血轉(zhuǎn)化組和非出血轉(zhuǎn)化組病例數(shù)相應(yīng)的MMP-9值和logistic回歸分析的OR。使用RevMan4.2和SPSS11.0進(jìn)行統(tǒng)計(jì)學(xué)處理。
結(jié)果 　共納入6個(gè)研究，包括558例缺血性卒中患者，出血轉(zhuǎn)化者130例（23.3%）。納入研究的方法學(xué)質(zhì)量較高。各研究間異質(zhì)性較大（P lt;0.000 1）。組間血漿MMP-9水平?jīng)]有進(jìn)行Meta分析，多數(shù)研究認(rèn)為出血轉(zhuǎn)化組血漿MMP-9水平高于無出血轉(zhuǎn)化組，或某型出血轉(zhuǎn)化組血漿MMP-9水平高于無出血轉(zhuǎn)化組。亞組分析發(fā)現(xiàn)血漿MMP-9水平與出血轉(zhuǎn)化獨(dú)立相關(guān)， OR合并=14.45，95%CI（4.90，43.65）。
結(jié)論 　出血轉(zhuǎn)化或某亞型患者血漿MMP-9水平高于無出血轉(zhuǎn)化者；MMP-9可能是出血轉(zhuǎn)化的獨(dú)立危險(xiǎn)因素；但現(xiàn)有的研究病例數(shù)較少，上述發(fā)現(xiàn)還需要更多的研究予以證實(shí)。

引用本文： 曹心慧,劉 鳴,吳 波. 血漿基質(zhì)金屬蛋白酶-9與缺血性卒中出血轉(zhuǎn)化關(guān)系的系統(tǒng)評價(jià). 中國循證醫(yī)學(xué)雜志, 2006, 06(5): 361-369. doi: 復(fù)制

1. 王家良. 臨床流行病學(xué)-臨床科研設(shè)計(jì)、衡量與評價(jià). 第2版. 上海: 上海科學(xué)技術(shù)出版社; 2001. 297.
2. 劉建平. 非隨機(jī)研究的系統(tǒng)評價(jià)方法. 中國循證醫(yī)學(xué), 2001; 1(4): 239～243.
3. 劉建平. 非隨機(jī)研究的系統(tǒng)評價(jià)方法. 中國循證醫(yī)學(xué), 2002; 2(1): 44～48.
4. 談頌, 劉鳴. 血漿基質(zhì)金屬蛋白酶-9與急性缺血性卒中出血轉(zhuǎn)化關(guān)系的初步研究. 2005屆四川大學(xué)博士論文.
5. Hacke W, Kaste M, Fieschi C, et al. for the ECASS Study Group. Intravenous thrombolysis with recombinant tissue plasminogen activator for actue hemispheric stroke. JAMA, 1995; 274(13): 1017-1025.
6. The National Institute of Neurological Disorders and Stroke rtPA Stroke Study Group. Tissue plasminogen activator for actue ischemic stroke. N Engl J Med, 1995; 333(24): 1581-1587.
7. The Multicenter Acute Stroke TrialEurope Study Group. Thrombolytic therapy with Streptokinasein acute ischemic stroke. N Engl J Med, 1996; 335(3): 145-150.
8. Rosenberg GA, Navratil M, Barone F, et al. Proteolytic casecade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Metab, 1996; 16(3): 360-366.
9. Gasche Y, Fujimura M, Morita- Fujimura Y, et al. Early appearance of activated matrix metalloprotienase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfuntion. J Cereb Blood Metab, 1999; 19(9): 1020-1028.
10. Wang JL. Clinical epidemiology-design, weigh, and evaluation of clinical research. Edi 2. Shanghai: Shanghai Publishing Company of Science and Technology; 2001. 297.
11. Liu JP. Method to systematic reviews of non-RCT. Chinese Journal of Evidence-Based Medicine, 2001; 1(4): 239-243.
12. Liu JP. Method to systematic reviews of non-RCT. Chinese Journal of Evidence-Based Medicine, 2002; 2(1): 44-48.
13. Castellanos M, Leila R, Serena J, et al. Plasma Cellular-Fibronectin Concentration Predicts Hemorrhagic Transformation After Thrombolytic Therapy in Acute Ischemic Stroke. Stroke, 2004; 35(7): 1671-1676.
14. Montaner J, Molina CA, Monasterio J, et al. Matrix Metalloproteinase-9 Pretreatment Level Predicts Intracranial Hemorrhagic Complications After Thrombolysis in Human Stroke. Circulation, 2003; 107(4): 598-603.
15. Montaner J, Fernández-Cadenas I, Molina CA, et al. Safety Profile of Tissue Plasminogen Activator Treatment Among Stroke Patients Carrying a Common Polymorphism (C-1562T) in the Promoter Region of the Matrix Metalloproteinase-9 Gene. Stroke, 2003; 34(12): 2851-2855.
16. Montaner J, Alvarez-Sabín J, Molina CA, et al. Matrix Metalloproteinase Expression Is Related to Hemorrhagic Transformation After Cardioembolic Stroke. Stroke, 2001; 32(12): 2762-2767.
17. Castellanos M, Leira R, Serena J, et al. Plasma Metalloproteinase-9 Concentration Predicts Hemorrhagic Transformation in Acute Ischemic Stroke. Stroke, 2003; 34(1): 40-46.
18. Tan S, Liu M. Study on relationship between plasma matrix metalloproteinase-9 level and hemorrhagic transformation in acute ischemic stroke. 2005 doctoral paper of Sichan university.
19. Kake W, Kaste M, Fieschi C, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous Alteplase in acute ischemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet, 1998; 352: 1245-1251.
  1. 1. 王家良. 臨床流行病學(xué)-臨床科研設(shè)計(jì)、衡量與評價(jià). 第2版. 上海: 上?？茖W(xué)技術(shù)出版社; 2001. 297.
  2. 2. 劉建平. 非隨機(jī)研究的系統(tǒng)評價(jià)方法. 中國循證醫(yī)學(xué), 2001; 1(4): 239～243.
  3. 3. 劉建平. 非隨機(jī)研究的系統(tǒng)評價(jià)方法. 中國循證醫(yī)學(xué), 2002; 2(1): 44～48.
  4. 4. 談頌, 劉鳴. 血漿基質(zhì)金屬蛋白酶-9與急性缺血性卒中出血轉(zhuǎn)化關(guān)系的初步研究. 2005屆四川大學(xué)博士論文.
  5. 5. Hacke W, Kaste M, Fieschi C, et al. for the ECASS Study Group. Intravenous thrombolysis with recombinant tissue plasminogen activator for actue hemispheric stroke. JAMA, 1995; 274(13): 1017-1025.
  6. 6. The National Institute of Neurological Disorders and Stroke rtPA Stroke Study Group. Tissue plasminogen activator for actue ischemic stroke. N Engl J Med, 1995; 333(24): 1581-1587.
  7. 7. The Multicenter Acute Stroke TrialEurope Study Group. Thrombolytic therapy with Streptokinasein acute ischemic stroke. N Engl J Med, 1996; 335(3): 145-150.
  8. 8. Rosenberg GA, Navratil M, Barone F, et al. Proteolytic casecade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Metab, 1996; 16(3): 360-366.
  9. 9. Gasche Y, Fujimura M, Morita- Fujimura Y, et al. Early appearance of activated matrix metalloprotienase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfuntion. J Cereb Blood Metab, 1999; 19(9): 1020-1028.
  10. 10. Wang JL. Clinical epidemiology-design, weigh, and evaluation of clinical research. Edi 2. Shanghai: Shanghai Publishing Company of Science and Technology; 2001. 297.
  11. 11. Liu JP. Method to systematic reviews of non-RCT. Chinese Journal of Evidence-Based Medicine, 2001; 1(4): 239-243.
  12. 12. Liu JP. Method to systematic reviews of non-RCT. Chinese Journal of Evidence-Based Medicine, 2002; 2(1): 44-48.
  13. 13. Castellanos M, Leila R, Serena J, et al. Plasma Cellular-Fibronectin Concentration Predicts Hemorrhagic Transformation After Thrombolytic Therapy in Acute Ischemic Stroke. Stroke, 2004; 35(7): 1671-1676.
  14. 14. Montaner J, Molina CA, Monasterio J, et al. Matrix Metalloproteinase-9 Pretreatment Level Predicts Intracranial Hemorrhagic Complications After Thrombolysis in Human Stroke. Circulation, 2003; 107(4): 598-603.
  15. 15. Montaner J, Fernández-Cadenas I, Molina CA, et al. Safety Profile of Tissue Plasminogen Activator Treatment Among Stroke Patients Carrying a Common Polymorphism (C-1562T) in the Promoter Region of the Matrix Metalloproteinase-9 Gene. Stroke, 2003; 34(12): 2851-2855.
  16. 16. Montaner J, Alvarez-Sabín J, Molina CA, et al. Matrix Metalloproteinase Expression Is Related to Hemorrhagic Transformation After Cardioembolic Stroke. Stroke, 2001; 32(12): 2762-2767.
  17. 17. Castellanos M, Leira R, Serena J, et al. Plasma Metalloproteinase-9 Concentration Predicts Hemorrhagic Transformation in Acute Ischemic Stroke. Stroke, 2003; 34(1): 40-46.
  18. 18. Tan S, Liu M. Study on relationship between plasma matrix metalloproteinase-9 level and hemorrhagic transformation in acute ischemic stroke. 2005 doctoral paper of Sichan university.
  19. 19. Kake W, Kaste M, Fieschi C, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous Alteplase in acute ischemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet, 1998; 352: 1245-1251.