周翔 1 , 喻琴梅 2 , 劉挺 2 , 王紅 1 , 莊華 1 , 羅燕 1 , 彭玉蘭 1
  • 四川大學(xué)華西醫(yī)院（成都，610041）1超聲科，2血液科和血液學(xué)研究室;

目的通過(guò)體外實(shí)驗(yàn)，利用正交設(shè)計(jì)方法，探討微泡強(qiáng)化聲溶栓的主要影響因素，并確定微泡強(qiáng)化聲溶栓體外實(shí)驗(yàn)的優(yōu)選條件。 方法取50只SD雌性大鼠外周血制備標(biāo)準(zhǔn)血漿后，以100 μL標(biāo)準(zhǔn)血漿與25 μL凝血酶（0.15 U/ μL）混勻，置于37℃恒溫水浴箱分別孵育3、6、12、24 h，制備相應(yīng)栓齡血栓；建立體外溶栓模型。確定4個(gè)物理參數(shù)：超聲輸出能量（因素A：5%、25%、50%、100%），微泡量（因素B：50、100、200、400 μL）；尿激酶濃度（因素C：100、200、400、800 U/mL）；超聲處理溶栓時(shí)間（因素D：10、20、30、40 min），進(jìn)行四因素四水平正交實(shí)驗(yàn)，建立L16（45）正交表。低頻診斷超聲頻率為1.82 MHz，進(jìn)行體外溶栓實(shí)驗(yàn)。組織學(xué)及掃描電鏡觀察溶栓前后血栓結(jié)構(gòu)。溶栓前后進(jìn)行血栓稱重，計(jì)算溶栓率，并進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果組織學(xué)及掃描電鏡觀察各栓齡血栓溶栓后，血栓纖維網(wǎng)架被破壞。體外條件下最優(yōu)溶栓條件組合為C4-D4-A1-B4，即：尿激酶濃度800 U/mL、溶栓時(shí)間40 min、超聲輸出能量5%、微泡量400 μL。4個(gè)物理參數(shù)對(duì)各栓齡血栓溶栓效果均有顯著影響（P  lt; 0.05），其中尿激酶濃度對(duì)溶栓率影響最顯著。血栓栓齡顯著影響溶栓效果，差異有統(tǒng)計(jì)學(xué)意義（P  lt; 0.05）。 結(jié)論微泡強(qiáng)化聲溶栓效果可靠，尿激酶起主導(dǎo)溶栓作用。低超聲輸出能量、高造影劑微泡量、長(zhǎng)超聲輻照時(shí)間以及短栓齡有助于溶栓效果的提高。

引用本文： 周翔,喻琴梅,劉挺,王紅,莊華,羅燕,彭玉蘭. 微泡強(qiáng)化聲溶栓物理?xiàng)l件優(yōu)化的正交分析. 中國(guó)修復(fù)重建外科雜志, 2012, 26(9): 1098-1101. doi: 復(fù)制

1. Shaw GJ, Bavani N, Dhamija A, et al. Effect of mild hypothermia on the thrombolytic efficacy of 120 kHz ultrasound enhanced thrombolysis in an in-vitro human clot model. Thromb Res, 2006, 117(5): 603-608.
2. Holland CK, Vaidya SS, Datta S, et al. Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model. Thromb Res, 2008, 121(5): 663-673.
3. Mehta RH, Stebbins A, Lopes RD, et al. Race, bleeding, and outcomes in STEMI patients treated with fibrinolytic therapy. Am J Med, 2011, 124(1): 48-57.
4. Stein PD, Matta F, Steinberger DS, et al. Intracerebral hemorrhage with thrombolytic therapy for acute pulmonary embolism. Am J Med, 2012, 125(1): 50-56.
5. Donnan GA, Davis SM, Parsons MW, et al. How to make better use of thrombolytic therapy in acute ischemic stroke. Nat Rev Neurol, 2011, 7(7): 400-409.
6. Torno MD, Kaminski MD, Xie Y, et al. Improvement of in vitro thrombolysis employing magnetically-guided microspheres. Thromb Res, 2008, 121(6): 799-811.
7. Hua X, Liu P, Gao YH, et al. Construction of thrombus-targeted microbubbles carrying tissue plasminogen activator and their in vitro thrombolysis efficacy: a primary research. J Thromb Thrombolysis, 2010, 30(1): 29-35.
8. Culp WC, Erdem E, Roberson PK, et al. Microbubble potentiated ultrasound as a method of stroke therapy in a pig model: preliminary findings. J Vasc Interv Radiol, 2003, 14(11): 1433-1436.
9. Culp WC, Porter TR, Lowery J, et al. Intracranial clot lysis with intravenous microbubbles and transcranial ultrasound in swine. Stroke, 2004, 35(10): 2407-2411.
10. Tsivgoulis G, Eggers J, Ribo M, et al. Safety and efficacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies. Stroke, 2010, 41(2): 280-287.
11. Siegel RJ, Luo H. Ultrasound thrombolysis. Ultrasonics, 2008, 48(4): 312-320.
12. Pfaffenberger S, Devcic-Kuhar B, Kollmann C, et al. Can a commercial diagnostic ultrasound device accelerate thrombolysis? An in vitro skull model. Stroke, 2005, 36(1): 124-128.
13. Alexandrov AV. Ultrasound enhanced thrombolysis for stroke. Int J Stroke, 2006, 1(1): 26-29.
14. 陳冉, 任衛(wèi)東, 吳瑕, 等. 診斷超聲介導(dǎo)自制微泡造影劑的溶栓效應(yīng)及參數(shù)優(yōu)化體外實(shí)驗(yàn)研究. 中國(guó)醫(yī)學(xué)影像技術(shù), 2008, 24(1): 9-12.
15. Kirchhof K, Welzel T, Zoubaa S, et al. New method of embolus preparation for standardized embolic stroke in rabbits. Stroke, 2002, 33(9): 2329-2333.
16. Trübestein G, Engel C, Etzel F, et al. Thrombolysis by ultrasound. Clin Sci Mol Med Suppl, 1976, 3: 697s-698s.
17. Prokop AF, Soltani A, Roy RA. Cavitational mechanisms in ultrasound-accelerated fibrinolysis. Ultrasound Med Biol, 2007, 33(6): 924-933.
18. 華興, 高云華, 劉政, 等. 輻照時(shí)間與血栓凝齡對(duì)超聲波體外溶栓的影響. 臨床超聲醫(yī)學(xué)雜志, 2007, 9(4): 193-195.
19. Xie F, Everbach EC, Gao S, et al. Effects of attenuation and thrombus age on the success of ultrasound and microbubble-mediated thrombus dissolution. Ultrasound Med Biol, 2011, 37 (2): 280-288.
20. Beythien C, Terres W, Gutensohn K, et al. Thrombus age as a determinant of lysis efficacy of in vitro produced platelet-fibrin thrombi. Z Kardiol, 1996, 85(9): 661-667.
21. Krueger K, Deissler P, Coburger S, et al. How thrombus model impacts the in vitro study of interventional thrombectomy procedures. Invest Radiol, 2004, 39(10): 641-648.
22. 杜寶琮, 杜寶民, 翟桂琴. 體外治療量超聲對(duì)血栓溶解效應(yīng)的影響. 中華物理醫(yī)學(xué)與康復(fù)雜志, 2002, 24(7): 417-420.
  1. 1. Shaw GJ, Bavani N, Dhamija A, et al. Effect of mild hypothermia on the thrombolytic efficacy of 120 kHz ultrasound enhanced thrombolysis in an in-vitro human clot model. Thromb Res, 2006, 117(5): 603-608.
  2. 2. Holland CK, Vaidya SS, Datta S, et al. Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model. Thromb Res, 2008, 121(5): 663-673.
  3. 3. Mehta RH, Stebbins A, Lopes RD, et al. Race, bleeding, and outcomes in STEMI patients treated with fibrinolytic therapy. Am J Med, 2011, 124(1): 48-57.
  4. 4. Stein PD, Matta F, Steinberger DS, et al. Intracerebral hemorrhage with thrombolytic therapy for acute pulmonary embolism. Am J Med, 2012, 125(1): 50-56.
  5. 5. Donnan GA, Davis SM, Parsons MW, et al. How to make better use of thrombolytic therapy in acute ischemic stroke. Nat Rev Neurol, 2011, 7(7): 400-409.
  6. 6. Torno MD, Kaminski MD, Xie Y, et al. Improvement of in vitro thrombolysis employing magnetically-guided microspheres. Thromb Res, 2008, 121(6): 799-811.
  7. 7. Hua X, Liu P, Gao YH, et al. Construction of thrombus-targeted microbubbles carrying tissue plasminogen activator and their in vitro thrombolysis efficacy: a primary research. J Thromb Thrombolysis, 2010, 30(1): 29-35.
  8. 8. Culp WC, Erdem E, Roberson PK, et al. Microbubble potentiated ultrasound as a method of stroke therapy in a pig model: preliminary findings. J Vasc Interv Radiol, 2003, 14(11): 1433-1436.
  9. 9. Culp WC, Porter TR, Lowery J, et al. Intracranial clot lysis with intravenous microbubbles and transcranial ultrasound in swine. Stroke, 2004, 35(10): 2407-2411.
  10. 10. Tsivgoulis G, Eggers J, Ribo M, et al. Safety and efficacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies. Stroke, 2010, 41(2): 280-287.
  11. 11. Siegel RJ, Luo H. Ultrasound thrombolysis. Ultrasonics, 2008, 48(4): 312-320.
  12. 12. Pfaffenberger S, Devcic-Kuhar B, Kollmann C, et al. Can a commercial diagnostic ultrasound device accelerate thrombolysis? An in vitro skull model. Stroke, 2005, 36(1): 124-128.
  13. 13. Alexandrov AV. Ultrasound enhanced thrombolysis for stroke. Int J Stroke, 2006, 1(1): 26-29.
  14. 14. 陳冉, 任衛(wèi)東, 吳瑕, 等. 診斷超聲介導(dǎo)自制微泡造影劑的溶栓效應(yīng)及參數(shù)優(yōu)化體外實(shí)驗(yàn)研究. 中國(guó)醫(yī)學(xué)影像技術(shù), 2008, 24(1): 9-12.
  15. 15. Kirchhof K, Welzel T, Zoubaa S, et al. New method of embolus preparation for standardized embolic stroke in rabbits. Stroke, 2002, 33(9): 2329-2333.
  16. 16. Trübestein G, Engel C, Etzel F, et al. Thrombolysis by ultrasound. Clin Sci Mol Med Suppl, 1976, 3: 697s-698s.
  17. 17. Prokop AF, Soltani A, Roy RA. Cavitational mechanisms in ultrasound-accelerated fibrinolysis. Ultrasound Med Biol, 2007, 33(6): 924-933.
  18. 18. 華興, 高云華, 劉政, 等. 輻照時(shí)間與血栓凝齡對(duì)超聲波體外溶栓的影響. 臨床超聲醫(yī)學(xué)雜志, 2007, 9(4): 193-195.
  19. 19. Xie F, Everbach EC, Gao S, et al. Effects of attenuation and thrombus age on the success of ultrasound and microbubble-mediated thrombus dissolution. Ultrasound Med Biol, 2011, 37 (2): 280-288.
  20. 20. Beythien C, Terres W, Gutensohn K, et al. Thrombus age as a determinant of lysis efficacy of in vitro produced platelet-fibrin thrombi. Z Kardiol, 1996, 85(9): 661-667.
  21. 21. Krueger K, Deissler P, Coburger S, et al. How thrombus model impacts the in vitro study of interventional thrombectomy procedures. Invest Radiol, 2004, 39(10): 641-648.
  22. 22. 杜寶琮, 杜寶民, 翟桂琴. 體外治療量超聲對(duì)血栓溶解效應(yīng)的影響. 中華物理醫(yī)學(xué)與康復(fù)雜志, 2002, 24(7): 417-420.