TARGETED COMBINATION AND ANTI-INFLAMMATORY EFFECTS OF ANTI-INTERCELLULAR ADHESION MOLECULE 1 TARGETED PERFLUOROOCTYLBROMIDE PARTICLES ON MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN RAT MODEL_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

SHANG Yanwen ¹ , TANG Hong ¹ , WEI Xin ¹ , HOU Jianglong ² , WANG Lian ³ , LI Guohua ⁴ , SONG Haibo ⁴ , FANG Hua ⁴

1Department of Cardiology, 2Department of Cardiothoracic Surgery, 4Department of Anesthesia, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;;
3Department of Pathology, West China Stomatological Hospital, Sichuan University. Corresponding author: TANG Hong, E-mail: hxyyth@gmail.com;

Corresponding author：

Keywords：

Myocardial ischemia-reperfusion injury; Perfluorooctylbromide; Intercellular adhesion molecule 1; Rat

DOI：

10.7507/1002-1892.20130078

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Objective To investigate the targeted combination and anti-inflammatory effects of anti-intercellular adhesion molecule 1 (ICAM-1) targeted perfluorooctylbromide (PFOB) particles on myocardial ischemia-reperfusion injury in rat model. Methods Seventy-six adult Sprague Dawley rats (male or female, weighing 250-300 g) were selected for experiment. The models of myocardial ischemia-reperfusion injury were established by ligating the left anterior descending coronary artery for 30 minutes in 30 rats. The expression of ICAM-1 protein was detected by immunohistochemistry staining at 6 hours after reperfusion, and the normal myocardium of 10 rats were harvested as control; then the content of interleukin 8 (IL-8) in serum was tested every 6 hours from 6 hours to 48 hours after reperfusion. The other 36 rats were randomly divided into 6 groups (n=6): ischemia-reperfusion injury model/targeted PFOB particles group (group A), ischemia-reperfusion injury model/untargeted PFOB group (group B), normal control/targeted PFOB particles group (group C), normal control/untargeted PFOB particles group (group D), ischemia-reperfusion injury model/normal saline group (group E), and sham operation group (group F). The ischemia-reperfusion injury models were established in groups A, B, and E; while a thread crossed under the coronary artery, which was not ligated after open-chest in group F. After 6 hours of reperfusion, 1 mL of corresponding PFOB particles was injected through juglar vein in groups A, B, C, and D, while 1 mL of nomal saline was injected in group E. Ultrasonography was performed in groups A, B, C, and D before and after injection. The targeted combination was tested by fluorescence microscope. The content of IL-8 was tested after 6 and 24 hours of reperfusion by liquid chip technology in groups A, B, E, and F. Results After 6 hours of reperfusion, the expression of ICAM-1 protein significantly increased in the anterior septum and left ventricular anterior wall of the rat model. The content of IL-8 rised markedly from 6 hours after reperfusion, and reached the peak at 24 hours. Ultrasonography observation showed no specific acoustic enhancement after injection of PFOB particles in groups A, B, C, and D. Targeted combination was observed in the anterior septum and left ventricular anterior wall in group A, but no targeted combination in groups B, C, and D. There was no significant difference in the content of IL-8 among groups A, B, and E after 6 hours of reperfusion (P gt; 0.05), but the content in groups A, B, and E was significantly higher than that in group F (P lt; 0.05). After 24 hours of reperfusion, no sigificant difference was found in the content of IL-8 between groups A and B (P gt; 0.05), but the content of IL-8 in groups A and B were significantly lower than that in group E (P lt; 0.05). Conclusion Anti-ICAM-1 targeted PFOB particles can target to bind and pretect injured myocardium of rat by its anti-inflammation effects.

Citation： SHANG Yanwen,TANG Hong,WEI Xin,HOU Jianglong,WANG Lian,LI Guohua,SONG Haibo,FANG Hua. TARGETED COMBINATION AND ANTI-INFLAMMATORY EFFECTS OF ANTI-INTERCELLULAR ADHESION MOLECULE 1 TARGETED PERFLUOROOCTYLBROMIDE PARTICLES ON MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN RAT MODEL. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(3): 340-344. doi: 10.7507/1002-1892.20130078 Copy

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.
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7.	何佰永, 李赵欢, 唐红, 等. 液态氟碳脂质微球靶向损伤心肌细胞的体外实验. 生物医学工程学杂志, 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时ICAM-1表达变化规律及艾司洛尔的影响. 中国康复理论与实践, 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. 韦馨. 抗ICAM-1液态氟碳纳米微球靶向损伤心肌细胞的体外实验及其细胞毒性作用研究. 成都: 四川大学临床医学院, 2012.
7. 何佰永, 李赵欢, 唐红, 等. 液态氟碳脂质微球靶向损伤心肌细胞的体外实验. 生物医学工程学杂志, 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时ICAM-1表达变化规律及艾司洛尔的影响. 中国康复理论与实践, 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.

Chinese Journal of Reparative and Reconstructive Surgery

TARGETED COMBINATION AND ANTI-INFLAMMATORY EFFECTS OF ANTI-INTERCELLULAR ADHESION MOLECULE 1 TARGETED PERFLUOROOCTYLBROMIDE PARTICLES ON MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN RAT MODEL

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