超声辐射力结合靶向超声微泡评价小鼠肾缺血再灌注损伤
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摘要
目的探讨超声辐射力促进靶向微泡粘附提高肾缺血再灌注(IR)损伤检测的敏感性及可行性。方法制作小鼠肾缺血再灌注模型及正常对照组,并根据再灌注后1、3、6、12、24 h分别分为IRlh、IR3 h、IR6 h、IR12 h、IR24 h组。各组再根据有无超声辐射力作用随机分为单击靶向微泡(MBICAM)组和靶向微泡+超声辐射力组(MBICAM+USRF)组。结果 MBICAM组和MB_(ICAM+USRF)组在对照组肾脏均未见明显显影增强,肾脏声强度(VI)值无显著差异(6.47±0.42对6.45±0.62,P=0.923)。肾脏IR损伤不同时间窗下均可见显影增强,并且随着时间的推移,显影强度逐渐增高。MB_(ICAM+USRF)组缺血再灌注各时间窗肾脏VI值较MBICAM组显著增大,两者之间均存在显著性差异(P均=0.000)。IR12 h和IR24 h VI值之间无显著差异(P=1.000),其余各组之间均存在显著差异(P<0.05)。结论应用超声辐射力联合携抗细胞间黏附分子1单抗靶向微泡可提高小鼠肾脏缺血再灌注损伤检测敏感性,可用于早期评价微血管炎症或相关的血管内皮反应
Objective To study the sensitivity and feasibility of detecting microvascular inflammation in renal ischemiareperfusion injury using microbubbles(MB) targeted to the intercellular adhesion molecule ICAM-1 and ultrasound radiation force(USRF). Methods Mouse models of kidney ischemia-reperfusion were randomized into 5 groups with reperfusion time of 1,3,6,12,and 24 h(IRlh,IR3 h,IR6 h,IR12 h,and IR24 h group,respectively). Each group was subdivided into targeted MB group(MBICAMgroup) and targeted MB+USRF group(MB_(ICAM+USRF) group). Kidney enhancement and the video intensity(VI) of the kidneys were compared among the groups. Results In normal mice in either MBICAMor MB_(ICAM+USRF) group,no obvious enhancement of the kidney or significant increase in VI of the kidneys was observed(P=0.923). The kidneys were enhanced in all the mice with renal ischemia-reperfusion injury,and with the passage of time,the enhancement increased progressively. VI in the kidneys of mice with renal ischemia-reperfusion injury in MB_(ICAM+USRF) group increased more significantly compared with the MBICAMgroup. Significant difference in the VI was noted among the groups with different perfusion time but not between IR12 h and IR24 h groups. Conclusion Microbubbles targeted to ICAM-1 combined with USRF can effectively evaluate renal ischemia-reperfusion injury in mice and can be used for early evaluation of microvascular inflammation and other endothelial responses.
Objective To study the sensitivity and feasibility of detecting microvascular inflammation in renal ischemiareperfusion injury using microbubbles(MB) targeted to the intercellular adhesion molecule ICAM-1 and ultrasound radiation force(USRF). Methods Mouse models of kidney ischemia-reperfusion were randomized into 5 groups with reperfusion time of 1,3,6,12,and 24 h(IRlh,IR3 h,IR6 h,IR12 h,and IR24 h group,respectively). Each group was subdivided into targeted MB group(MBICAMgroup) and targeted MB+USRF group(MB_(ICAM+USRF) group). Kidney enhancement and the video intensity(VI) of the kidneys were compared among the groups. Results In normal mice in either MBICAMor MB_(ICAM+USRF) group,no obvious enhancement of the kidney or significant increase in VI of the kidneys was observed(P=0.923). The kidneys were enhanced in all the mice with renal ischemia-reperfusion injury,and with the passage of time,the enhancement increased progressively. VI in the kidneys of mice with renal ischemia-reperfusion injury in MB_(ICAM+USRF) group increased more significantly compared with the MBICAMgroup. Significant difference in the VI was noted among the groups with different perfusion time but not between IR12 h and IR24 h groups. Conclusion Microbubbles targeted to ICAM-1 combined with USRF can effectively evaluate renal ischemia-reperfusion injury in mice and can be used for early evaluation of microvascular inflammation and other endothelial responses.
引文
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[13]Ren KX,Jin C,Ma PF,et al.Ginsenoside Rd alleviates mouse acute renal ischemia/reperfusion injury by modulating macrophage phenotype[J].J Ginseng Res,2016,40(2):196-202.
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[16]纪丽景,王宝平,罗利红,等.细胞间黏附分子-1靶向微泡超声造影成像评价肾移植后急性排异反应[J].中华超声影像学杂志,2011,20(12):1070-3.
[17]杨阳,乔璐,严飞,等.超声辐射力推移靶向微泡的参数设置研究[J].中国超声医学杂志,2015,31(2):170-3.
[18]Hussein A,El-Dken ZH,Barakat N,et al.Renal ischaemia/reperfusion injury:possible role of aquaporins[J].Acta Physiologica,2012,204(3):308-16.
[19]van Rooij T,Daeichin V,Skachkov I,et al.Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy[J].Int J Hyperthermia,2015,31(2):90-106.
[20]Wang SY,Wang CY,Unnikrishnan S,et al.Optical verification of microbubble response to acoustic radiation force in large vessels with in vivo results[J].Invest Radiol,2015,50(11):772-84.
[21]Herbst EB,Unnikrishnan S,Wang SA,et al.The use of acoustic radiation force Decorrelation-Weighted pulse inversion for enhanced ultrasound contrast imaging[J].Invest Radiol,2017,52(2):95-102.
[2]Li M,Luo Z,Chen X,et al.Use of contrast-enhanced ultrasound to monitor rabbit renal ischemia-reperfusion injury and correlations between time-intensity curve parameters and renal ICAM-1expression[J].Clin Hemorheol Microcirc,2015,59(2):123-31.
[3]吴爵非,Yang L,宾建平,等.在生理血流条件下靶向超声微泡对P-选择素的靶向黏附效能[J].中国医学影像技术,2008,24(7):981-4.
[4]Takalkar AM,Klibanov AL,Rychak JJ,et al.Binding and detachment dynamics of microbubbles targeted to P-selectin under controlled shear flow[J].J Control Release,2004,96(3):473-82.
[5]王宝平,吴凤林,纪丽景,等.超声辐射力促靶向微泡黏附的在体实验研究[J].中华超声影像学杂志,2013,22(3):255-8.
[6]Rychak JJ,Klibanov AL,Ley KF.Enhanced targeting of ultrasound contrast agents using acoustic radiation force[J].Ultrasound Med Biol,2007,33(7):1132-9.
[7]Schutt EG,Klein DH,Mattrey RM,et al.Injectable microbubbles as contrast agents for diagnostic ultrasound imaging:The key role of perfluorochemicals[J].Angew Chem Int Ed Engl,2003,42(28):3218-35.
[8]Lanza GM,Wickline SA.Targeted ultrasonic contrast agents for molecular imaging and therapy[J].Prog Cardiovasc Dis,2001,44(1):13-31.
[9]Lindner JR,Song J,Christiansen J,et al.Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin[J].Circulation,2001,104(17):2107-12.
[10]Liu J,Zhang P,Liu P,et al.Endothelial adhesion of targeted microbubbles in both small and great vessels using ultrasound radiation force[J].Mol Imaging,2012,11(1):58-66.
[11]Bataille A,Abbas S,Semoun O,et al.Plasma neutrophil GelatinaseAssociated lipocalin in kidney transplantation and early renal function prediction[J].Transplantation,2011,92(9):1024-30.
[12]De Greef KE,Ysebaert DK,Persy V,et al.Icam-1 expression and leukocyte accumulation in inner stripe of outer medulla in early phase of ischemic compared to hgcl2-induced ARF[J].Kidney Int,2003,63(5):1697-707.
[13]Ren KX,Jin C,Ma PF,et al.Ginsenoside Rd alleviates mouse acute renal ischemia/reperfusion injury by modulating macrophage phenotype[J].J Ginseng Res,2016,40(2):196-202.
[14]刘百成,刘荣耀.大鼠肾缺血再灌注损伤中ICAM-1表达的变化[J].中国中西医结合肾病杂志,2006,7(8):419-21.
[15]Tong F,Luo L,Liu DJ.Effect of intervention in mast cell function before reperfusion on renal Ischemia-Reperfusion injury in rats[J].Kidney Blood Press Res,2016,41(3):335-44.
[16]纪丽景,王宝平,罗利红,等.细胞间黏附分子-1靶向微泡超声造影成像评价肾移植后急性排异反应[J].中华超声影像学杂志,2011,20(12):1070-3.
[17]杨阳,乔璐,严飞,等.超声辐射力推移靶向微泡的参数设置研究[J].中国超声医学杂志,2015,31(2):170-3.
[18]Hussein A,El-Dken ZH,Barakat N,et al.Renal ischaemia/reperfusion injury:possible role of aquaporins[J].Acta Physiologica,2012,204(3):308-16.
[19]van Rooij T,Daeichin V,Skachkov I,et al.Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy[J].Int J Hyperthermia,2015,31(2):90-106.
[20]Wang SY,Wang CY,Unnikrishnan S,et al.Optical verification of microbubble response to acoustic radiation force in large vessels with in vivo results[J].Invest Radiol,2015,50(11):772-84.
[21]Herbst EB,Unnikrishnan S,Wang SA,et al.The use of acoustic radiation force Decorrelation-Weighted pulse inversion for enhanced ultrasound contrast imaging[J].Invest Radiol,2017,52(2):95-102.