抗細胞間黏附分子1靶向液態氟碳微球對大鼠缺血再灌注損傷心肌的靶向結合和抗炎作用的研究_《中國修復重建外科雜志》

作者：

尚艷文 ¹ , 唐紅 ¹ , 韋馨 ¹ , 侯江龍 ² , 王煉 ³ , 李國華 ⁴ , 宋海波 ⁴ , 方華 ⁴

四川大學華西醫院（成都，610041）1心內科，2胸心外科，4麻醉科;;
3 四川大學華西口腔醫院病理科;

關鍵詞：

心肌缺血再灌注損傷液態氟碳細胞間黏附分子1 大鼠

DOI：

10.7507/1002-1892.20130078

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目的探討抗細胞間黏附分子 1（intercellular adhesion molecule 1，ICAM-1）靶向液態氟碳（per-fluorooctylbromide，PFOB）微球對大鼠缺血再灌注損傷心肌的靶向結合和抗炎作用。方法取成年SD大鼠76只，雌雄不限，體重250～300 g。取30只采用結扎冠狀動脈左前降支30 min方法制備心肌缺血再灌注損傷模型，免疫組織化學染色觀察缺血再灌注6 h心肌細胞表面ICAM-1蛋白表達情況，以10只正常大鼠作為對照；液相芯片技術檢測缺血再灌注6、12、18、24、30、36、42、48 h血清中IL-8含量。另取36只大鼠隨機分為6組（n=6）：心肌缺血再灌注/靶向PFOB微球組（A組）、心肌缺血再灌注/普通PFOB微球組（B組）、正常大鼠/靶向PFOB微球組（C組）、正常大鼠/普通PFOB微球組（D組）、心肌缺血再灌注/生理鹽水組（E組）、假手術組（F組）。A、B、E組大鼠同法建立心肌缺血再灌注損傷模型；F組開胸后在冠狀動脈下穿線但不結扎。缺血再灌注6 h后，A、B、C、D組經頸靜脈注入1 mL對應的PFOB微球，E組注入1 mL生理鹽水。超聲觀察A、B、C、D組注入PFOB微球前后心肌顯像情況；熒光顯微鏡觀察A、B、C、D組心臟冰凍切片微球結合情況；液相芯片技術檢測A、B、E、F組缺血再灌注6 h及24 h血清中IL-8含量。結果缺血再灌注6 h后大鼠心肌細胞表面ICAM-1蛋白表達以前間隔和左室前壁較明顯；IL-8含量自缺血再灌注6 h起開始增高，24 h達峰值。注入PFOB微球后至缺血再灌注24 h A、B、C、D組超聲觀察均未見明確受損心肌靶向顯影；熒光顯微鏡下A組前間隔和左室前壁心肌細胞核周圍可見綠染的靶向PFOB微球， B、C、D組均未見綠色熒光。缺血再灌注6 h，A、B、E組間IL-8含量相似（P gt; 0.05），但均高于F組（P lt; 0.05）；24 h時A、B組間IL-8含量相似（P gt; 0.05），均低于E組（P lt; 0.05）。結論抗ICAM-1靶向PFOB微球可靶向結合大鼠缺血再灌注損傷心肌，通過其抗炎作用保護受損心肌。

引用本文： 尚艷文,唐紅,韋馨,侯江龍,王煉,李國華,宋海波,方華. 抗細胞間黏附分子1靶向液態氟碳微球對大鼠缺血再灌注損傷心肌的靶向結合和抗炎作用的研究. 中國修復重建外科雜志, 2013, 27(3): 340-344. doi: 10.7507/1002-1892.20130078 復制

1.	Linder JR. Contrast ultrasound molecular imaging of inflammation in cardiovascular disease. Cardiovasc Res, 2009, 84(2): 182-189.
2.	Lanza GM, Wallace KD, Scott MJ, et al. A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation, 1996, 94(12): 3334-3340.
3.	Marsh JN, Hall CS, Scott MJ, et al. Improvements in the ultrasonic contrast of targeted perfiuorocarbon nanoparticles using an acoustic transmission line model. IEEE Trans Ultrason Ferroelectr Freq Control, 2002, 49(1): 29-38.
4.	Rempf C, Standl T, Gottschalk A, et al. Effects of a prophylactic or therapeutic application of perflubron emulsion on myocardial ischaemia-reperfusion injury in rats. Eur J Anaesthesiol, 2008, 25(10): 850-859.
5.	Gale SC, Gorman GD, Copeland JG, et al. Perfiubron emulsion prevents PMN activation and improves myocardial functional recovery after cold ischemia and reperfusion. J Surg Res, 2007, 138(1): 135-140.
6.	韋馨. 抗ICAM-1液態氟碳納米微球靶向損傷心肌細胞的體外實驗及其細胞毒性作用研究. 成都: 四川大學臨床醫學院, 2012.
7.	何佰永, 李趙歡, 唐紅, 等. 液態氟碳脂質微球靶向損傷心肌細胞的體外實驗. 生物醫學工程學雜志, 2011, 28(6): 1170-1174.
8.	Oozawa S, Mori S, Kanke T, et al. Effects of HMGB1 on ischemia-reperfusion injury in the rat heart. Circ J, 2008, 72(7): 1178-1184.
9.	Zhang C, Xu X, Potter BJ, et al. TNF-alpha contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol, 2006, 26(3): 475-480.
10.	Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res, 2002, 53(1): 31-47.
11.	Jones SP, Trocha SD, Strange MB, et al. Leukocyte and endothelial cell adhesion molecules in a chronic murine model of myocardial reperfusion injury. Am J Physiol Heart Circ Physiol, 2000, 279(5): H2196-2201.
12.	Yan Y, Liao Y, Yang L, et al. Late-phase detection of recent myocardial ischaemia using ultrasound molecular imaging targeted to intercellular adhesion molecule-1. Cardiovasc Res, 2011, 89(1): 175-183.
13.	何坪, 司良毅. 老年大鼠心肌再灌注時ICAM-1表達變化規律及艾司洛爾的影響. 中國康復理論與實踐, 2002, 8(7): 423-425.
14.	Zhang M, Chen L. Status of cytokines in ischemia reperfusion induced heart injury. Cardiovasc Hematol Disord Drug Tragets, 2008, 8(3): 161-172.
15.	Oeffinger BE, Wheatley MA. Development and characterization of a nano-scale contrast agent. Ultrasonics, 2004, 42(1-9): 343-347.
16.	Barnett BP, Ruiz-Cabello J, Hota P, et al. Use of perfluorocarbon nanoparticles for non-invasive multimodal cell tracking of human pancreatic islets. Contrast Media Mol Imaging, 2011, 6(4): 251-259.
17.	Barnett BP, Ruiz-Cabello J, Hota P, et al. Fluorocapsules for improved function, immunoprotection, and visualization of cellular therapeutics with MR, US, and CT imaging. Radiology, 2011, 258(1): 182-191.
18.	Wickline SA, Lanza GM. Nanotechnology for molecular imaging and targeted therapy. Circulation, 2003, 107 (8): 1092-1095.
19.	Lanza GM, Abendschein DR, Hall CS, et al. In vivo molecular imaging of stretch-induced tissue factor in carotid arteries with ligand-targeted nanoparticles. J Am Soc Echocardiogr, 2000, 13(6): 608-614.
20.	Hughes MS, Marsh JN, Zhang H, et al. Characterization of digital waveforms using thermodynamic analogs: detection of contrast-targeted tissue in vivo. IEEE Trans Ultrason Ferroelectr Freq Control, 2006, 53(9): 1609-1616.
21.	Ngo FC, Hall CS, Marsh JN, et al. Evaluation of liquid perfiuorocarbon nanoparticles as a blood pool contrast agent utilizing power Doppler harmonic imaging. IEEE Ultrasonics Symposium Proceedings, 2000, 2(2): 1931-1934.
22.	Flegg MB, Poole CM, Whittaker AK, et al. Rayleigh theory of ultrasound scattering applied to liquid-filled contrast nanoparticles. Phys Med Biol, 2010, 55(11): 3061-3076.
23.	Rotta AT, Gunnarsson B, Fuhrman BP, et al. Perfiuorooctyl bromide (perfiubron) attenuates oxidative injury to biological and nonbiological systems. Pediatr Crit Care Med, 2003, 4(2): 233-238.
24.	Woods CM, Neslund G, Kornbrust E, et al. Perfiubron attenuates neutrophil adhesion to activated endothelial cells in vitro. Am J Physiol Lung Cell Mol Physiol, 2000, 278(5): L1008-1017.

1. Linder JR. Contrast ultrasound molecular imaging of inflammation in cardiovascular disease. Cardiovasc Res, 2009, 84(2): 182-189.
2. Lanza GM, Wallace KD, Scott MJ, et al. A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation, 1996, 94(12): 3334-3340.
3. Marsh JN, Hall CS, Scott MJ, et al. Improvements in the ultrasonic contrast of targeted perfiuorocarbon nanoparticles using an acoustic transmission line model. IEEE Trans Ultrason Ferroelectr Freq Control, 2002, 49(1): 29-38.
4. Rempf C, Standl T, Gottschalk A, et al. Effects of a prophylactic or therapeutic application of perflubron emulsion on myocardial ischaemia-reperfusion injury in rats. Eur J Anaesthesiol, 2008, 25(10): 850-859.
5. Gale SC, Gorman GD, Copeland JG, et al. Perfiubron emulsion prevents PMN activation and improves myocardial functional recovery after cold ischemia and reperfusion. J Surg Res, 2007, 138(1): 135-140.
6. 韋馨. 抗ICAM-1液態氟碳納米微球靶向損傷心肌細胞的體外實驗及其細胞毒性作用研究. 成都: 四川大學臨床醫學院, 2012.
7. 何佰永, 李趙歡, 唐紅, 等. 液態氟碳脂質微球靶向損傷心肌細胞的體外實驗. 生物醫學工程學雜志, 2011, 28(6): 1170-1174.
8. Oozawa S, Mori S, Kanke T, et al. Effects of HMGB1 on ischemia-reperfusion injury in the rat heart. Circ J, 2008, 72(7): 1178-1184.
9. Zhang C, Xu X, Potter BJ, et al. TNF-alpha contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol, 2006, 26(3): 475-480.
10. Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res, 2002, 53(1): 31-47.
11. Jones SP, Trocha SD, Strange MB, et al. Leukocyte and endothelial cell adhesion molecules in a chronic murine model of myocardial reperfusion injury. Am J Physiol Heart Circ Physiol, 2000, 279(5): H2196-2201.
12. Yan Y, Liao Y, Yang L, et al. Late-phase detection of recent myocardial ischaemia using ultrasound molecular imaging targeted to intercellular adhesion molecule-1. Cardiovasc Res, 2011, 89(1): 175-183.
13. 何坪, 司良毅. 老年大鼠心肌再灌注時ICAM-1表達變化規律及艾司洛爾的影響. 中國康復理論與實踐, 2002, 8(7): 423-425.
14. Zhang M, Chen L. Status of cytokines in ischemia reperfusion induced heart injury. Cardiovasc Hematol Disord Drug Tragets, 2008, 8(3): 161-172.
15. Oeffinger BE, Wheatley MA. Development and characterization of a nano-scale contrast agent. Ultrasonics, 2004, 42(1-9): 343-347.
16. Barnett BP, Ruiz-Cabello J, Hota P, et al. Use of perfluorocarbon nanoparticles for non-invasive multimodal cell tracking of human pancreatic islets. Contrast Media Mol Imaging, 2011, 6(4): 251-259.
17. Barnett BP, Ruiz-Cabello J, Hota P, et al. Fluorocapsules for improved function, immunoprotection, and visualization of cellular therapeutics with MR, US, and CT imaging. Radiology, 2011, 258(1): 182-191.
18. Wickline SA, Lanza GM. Nanotechnology for molecular imaging and targeted therapy. Circulation, 2003, 107 (8): 1092-1095.
19. Lanza GM, Abendschein DR, Hall CS, et al. In vivo molecular imaging of stretch-induced tissue factor in carotid arteries with ligand-targeted nanoparticles. J Am Soc Echocardiogr, 2000, 13(6): 608-614.
20. Hughes MS, Marsh JN, Zhang H, et al. Characterization of digital waveforms using thermodynamic analogs: detection of contrast-targeted tissue in vivo. IEEE Trans Ultrason Ferroelectr Freq Control, 2006, 53(9): 1609-1616.
21. Ngo FC, Hall CS, Marsh JN, et al. Evaluation of liquid perfiuorocarbon nanoparticles as a blood pool contrast agent utilizing power Doppler harmonic imaging. IEEE Ultrasonics Symposium Proceedings, 2000, 2(2): 1931-1934.
22. Flegg MB, Poole CM, Whittaker AK, et al. Rayleigh theory of ultrasound scattering applied to liquid-filled contrast nanoparticles. Phys Med Biol, 2010, 55(11): 3061-3076.
23. Rotta AT, Gunnarsson B, Fuhrman BP, et al. Perfiuorooctyl bromide (perfiubron) attenuates oxidative injury to biological and nonbiological systems. Pediatr Crit Care Med, 2003, 4(2): 233-238.
24. Woods CM, Neslund G, Kornbrust E, et al. Perfiubron attenuates neutrophil adhesion to activated endothelial cells in vitro. Am J Physiol Lung Cell Mol Physiol, 2000, 278(5): L1008-1017.

《中國修復重建外科雜志》

抗細胞間黏附分子1靶向液態氟碳微球對大鼠缺血再灌注損傷心肌的靶向結合和抗炎作用的研究

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《中國修復重建外科雜志》

抗細胞間黏附分子1靶向液態氟碳微球對大鼠缺血再灌注損傷心肌的靶向結合和抗炎作用的研究

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