[1]陆文烨 宋梦星 吴芬 夏敏 马占龙.磁共振靶向成像检测大鼠纤维化心肌中肌腱蛋白X表达的实验研究[J].心血管病学进展,2022,(5):463-468.[doi:10.16806/j.cnki.issn.1004-3934.2022.05.019]
 LU Wenye,SONG Mengxing,WU Fen,et al.Experimental Study on Expression of Tenascin-X in Fibrotic Myocardium of Rat by Magnatic Resonance Targeted Imaging[J].Advances in Cardiovascular Diseases,2022,(5):463-468.[doi:10.16806/j.cnki.issn.1004-3934.2022.05.019]
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磁共振靶向成像检测大鼠纤维化心肌中肌腱蛋白X表达的实验研究()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2022年5期
页码:
463-468
栏目:
出版日期:
2022-05-25

文章信息/Info

Title:
Experimental Study on Expression of Tenascin-X in Fibrotic Myocardium of Rat by Magnatic Resonance Targeted Imaging
作者:
陆文烨 宋梦星 吴芬 夏敏 马占龙
?南京医科大学第一附属医院放射科,江苏 南京 210029)
Author(s):
LU WenyeSONG MengxingWU FenXIA MinMA Zhanlong
(Department of Radiology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,Jiangsu,China)
关键词:
肌腱蛋白X心肌纤维化磁共振成像超微超顺磁性氧化铁
Keywords:
Tenascin-XMyocardial fibrosisMagnetic resonance imagingUltrasmall supperparamagnetic iron oxide
DOI:
10.16806/j.cnki.issn.1004-3934.2022.05.019
摘要:
目的 合成anti-TNX-USPIO探针,通过磁共振靶向成像检测大鼠心肌纤维化过程中肌腱蛋白X表达的可行性。方法 36只SD大鼠,随机选取12只作为空白对照组皮下注射生理盐水,24只皮下注射异丙肾上腺素,随机分为单纯对照组和实验组各12只,每日剂量均为5 mg/kg,连续注射7 d ,建立心肌纤维化大鼠模型。制备anti-TNX-USPIO合成探针,进行相关表征分析。实验组尾静脉注射anti-TNX-USPIO合成探针,空白对照组及单纯对照组分别尾静脉注射同等级剂量单纯超微超顺磁性氧化铁(USPIO),分别于打药前及打药10 h 后行磁共振成像,观察心肌信号强度变化,扫描完成后进行病理学观察。结果 注射异丙肾上腺素后,实验组及单纯对照组均显示为T2WI信号减低,心室壁变薄。空白对照组相对信号强度(rSI)为2.33±0.59,与实验组及单纯对照组的rSI(1.25±0.11)比较有统计学差异(P<0.001),表明实验组与单纯对照组心室壁纤维化改变,建模成功。注入探针后,实验组可见心肌信号强度减低,实验组打药后rSI为1.06±0.12,与打药前的rSI(1.21±0.11)比较有统计学差异(P<0.001);单纯对照组及空白对照组心肌信号强度未见明显减低,合成探针anti-TNX-USPIO对T2WI信号有明显减低作用。Masson染色显示单纯对照组及实验组心肌细胞间纤维组织大量增生,表明心肌纤维化改变。普鲁士蓝染色显示实验组心肌细胞内可见明显铁颗粒沉积,验证了纤维化心肌细胞中TNX抗体探针的存在。结论 纤维化心肌细胞中存在心肌表达TNX,anti-TNX-USPIO合成探针可实现大鼠心肌纤维化细胞中TNX体内靶向成像的检测目的,可将TNX作为心肌纤维化治疗的特异性靶点,为下一步临床研究提供思路。
Abstract:
Objective An anti-TNX-USPIO probe was synthesized to detect the feasibility of tenascin-X(TNX) protein exp ression in myocardial fibrosis by magnetic resonance targeted imaging. Methods Thirty-six SD rats were randomly selected as blank control group by subcutaneous injection of normal saline, and 24 rats by subcutaneous injection of isoproterenol were randomly divided into simple control group(n=12) and experimental group(n=12),with a daily dose of 5 mg/kg for 7 days,to establish myocardial fibrosis rat model. The anti-TNX-USPIO synthesis probe was prepared and the characterization analysis was carried out. In the experimental group,anti-TNX-USPIO synthetic probe was injected into the tail vein,and in the blank control group and the simple control group,USPIO with the same grade of dose was injected into the tail vein respectively. Magnatic resonance imaging was performed before administration and 10 hours after administration to observe changes in myocardial signal intensity,and pathological observation was 基金项目:国家自然科学基金面上项目(81971669)通信作者:马占龙,E-mail:mazhanlong@126.comperformed after scanning. Results After injection of isoproterenol,both the experimental group and the simple control group showed decreased T2WI signal and thinner ventricular wall. The relative signal intensity(rSI) in the blank control group was 2.33 ±0.59,which was statistically significant compared with the rSI(1.25±0.11) of the experimental group and the simple control group(P<0.001),indicating that the experimental group and the simple control group had fibrotic changes in ventricular wall,and the modeling was successful. After probe injection,the intensity of myocardial signal decreased in the experimental group,and the rSI of the experimental group after administration was 1.06±0.12, which was statistically significant compared with that before administration(1.21±0.11) (P<0.001). There was no significant decrease in the intensity of myocardial signal in the simple control group and the blank control group,and the synthetic probe anti-TNX-USPIO had a significant reduction in the intensity of T2WI signal. Masson staining showed a large number of fibrous tissues between the simple control group and the experimental group,indicating myocardial fibrosis changes. Prussian blue staining showed iron particles deposition in myocardial cells of the experimental group,confirming the presence of TNX antibody probes in fibrotic myocardial cells. Conclusion TNX protein is expressed in myocardium in fibrotic cardiomyocytes,and the anti-TNX-USPIO synthetic probe can achieve the purpose of in vivo targeted imaging detection of TNX protein in rat myocardial fibrosis cells,and TNX can be used as a specific target for the treatment of myocardial fibrosis,providing ideas for the next clinical study.

参考文献/References:

[1].Zareba KM,Truong VT,Mazur W,et al. T-wave and its association with myocardial fibrosis on cardiovascular magnetic resonance examination[J]. Ann Noninvasive Electrocardiol,2021,26(2):e12819.
[2].López B,Ravassa S,Moreno MU,et al. Diffuse myocardial fibrosis:mechanisms,diagnosis and therapeutic approaches[J]. Nat Rev Cardiol,2021,18(7):479-498.
[3].Prabhu SD,Frangogiannis NG. The biological basis forcardiacrepair aftermyocardialinfarction:from inflammation tofibrosis[J]. Circ Res,2016,119(1):91-112.
[4].郑育聪,陆敏杰,陈秀玉,等. 主动脉瓣关闭不全患者心肌纤维化的磁共振成像特征及其影响因素分析[J]. 中华心血管病杂志,2019,47(8):622-627.
[5].Mo F,Luo Y,Yan Y,et al. Are activated B cells involved in the process of myocardial fibrosis after acute myocardial infarction? An in vivo experiment[J]. BMC Cardiovasc Disord,2021,21(1):5.
[6].Ravassa S,González A,Bayés-Genís A,et al. Myocardial interstitial fibrosis in the era of precision medicine. Biomarker-based phenotyping for a personalized treatment[J]. Rev Esp Cardiol(Engl Ed),2020,73(3):248-254.
[7].Liang K,Baritussio A,Palazzuoli A,et al. Cardiovascularmagnetic resonance of myocardialfibrosis,edema,and infiltrates in heart failure[J]. Heart Fail Clin,2021,17(1):77-84.
[8].Valcourt U,Alcaraz LB,Exposito JY,et al. Tenascin-X:beyond the architectural function[J]. Cell Adh Migr,2015,9(1-2):154-165.
[9].Li L,Zhao Q,Kong W. Extracellular matrix remodeling and cardiac fibrosis[J]. Matrix Biol,2018,68-69:490-506.
[10].[10]宋佳成,李燕,孟欢,等. 肌腱蛋白C在急性心肌梗死中的表达及磁共振靶向成像的体内实验研究[J].中华老年心脑血管病杂志,2016,18(1):71-76.
[11].[11]Passaro F,Tocchetti CG,Spinetti G,et al. Targeting?fibrosis?in the falling heart with nanoparticles[J]. Adv Drug Deliv Rev,2021,174:461-481.
[12].[12]Aubert A,Mercier-Gouy P,Aguero S,et al. Latent TGF-β activation is a hallmark of the tenascin family[J]. Front Immunol,2021,12:613438.
[13].[13]Frangogiannis NG. Cardiac fibrosis:cell biological mechanisms,molecular pathways and therapeutic opportunities[J]. Mol Aspects Med,2019,65:70-99.
[14].[14]de Boer RA,de Keulenaer G,Bauersachs J,et al. Towards better definition,quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association(HFA) of the European Society of Cardiology[J]. Eur J Heart Fail,2019,21(3):272-285.
[15].[15]van Oorschot JW,Gho JM,van Hout GP,et al. Endogenous contrast MRI of cardiac fibrosis:beyond late gadolinium enhancement[J]. J Magn Reson Imaging,2015,41(5):1181-1189.
[16].[16]Miller WL.Tenascin-X-discovery and early research[J]. Front Immunol,2020,11:612497.
[17].[17]Alcaraz LB,Exposito JY,Chuvin N,et al. Tenascin-X promotes epithelial-to-mesenchymal transition by activating latent TGF-β[J]. J Cell Biol,2014,205(3):409-428.
[18].[18]Toth GB,Varallyay CG,Horvath A,et al. Current and potential imaging applications of ferumoxytol for magnetic resonance imaging[J]. Kidney Int,2017,92(1):47-66.
[19].[19]Merinopoulos I,Gunawardena T,Stirrat C,et al. Diagnostic applications of ultrasmall superparamagnetic particles of iron oxide for imaging myocardial and vascular inflammation[J]. JACC Cardiovasc Imaging,2021,14(6):1249-1264.
[20].[20]Bashir MR,Bhatti L,Marin D,et al. Emerging applications for ferumoxytol as a contrast agent in MRI[J]. J Magn Reson Imaging,2015,41(4):884-898.
[21].[21]Nguyen KL,Yoshida T,Kathuria-Prakash N,et al. Multicenter safety and practice for off-label diagnostic use of ferumoxytol in MRI[J]. Radiology,2019,293(3):554-564.
[22].[22]Lagan J,Naish JH,Simpson K,et al. Substrate for the myocardialinflammation—Heart failure hypothesis identified using novel?USPIOmethodology[J]. JACC Cardiovasc Imaging,2021,14(2):365-376.
[23].[23]Tada Y,Tachibana A,Heidary S,et al. Ferumoxytol-enhanced cardiovascular magnetic resonance detection of early stage acute myocarditis[J]. J Cardiovasc Magn Reson,2019,21(1):77.
[24].[24]Song J,Yu J,Li Y,et al. MR targeted imaging for the expression of tenascin-C in myocardial infarction in vivo[J]. J Magn Reson Imaging,2017,45(6):1668-1674.
[25].[25]Ferreira VM,Schulz-Menger J,Holmvang G,et al. Cardiovascular magnetic resonance in nonischemicmyocardial inflammation:expert recommendations[J]. J Am Coll Cardiol,2018,72(24):3158-3176.
[26].[26]Lu Y,Huang J,Neverova NV,et al. USPIOs as targeted contrast agents in cardiovascular magnetic resonance imaging[J]. Curr Cardiovasc Imaging Rep,2021,14(2):2.

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更新日期/Last Update: 2022-06-30