磁共振成像
磁共振成像
자공진성상
CHINESE JOURNAL OF MAGNETIC RESONANCE IMAGING
2014年
4期
296-301
,共6页
李然%方靖琴%陈晓%郭宇%艾华%张伟国
李然%方靖琴%陳曉%郭宇%艾華%張偉國
리연%방정금%진효%곽우%애화%장위국
神经胶质瘤%干细胞%内皮细胞%磁共振成像%动物,实验
神經膠質瘤%榦細胞%內皮細胞%磁共振成像%動物,實驗
신경효질류%간세포%내피세포%자공진성상%동물,실험
Glioma%Stem cell%Endothelial cells%Magnetic resonance imaging%Animal,laboratory
目的：探讨超微型超顺磁性氧化铁粒子(USPIO)标记的外源性内皮祖细胞(EPCs)在大鼠脑原位胶质瘤内的动态归巢特点，为利用磁性标记的EPCs作为MRI示踪细胞载体提供可行性的实验依据。材料与方法将SD大鼠分为假肿瘤组、肿瘤组和对照组3组，每组16只，肿瘤组和对照组在脑组织内移植C6胶质瘤细胞，而假肿瘤组仅刺破脑组织不移植胶质瘤细胞。待肿瘤组和假肿瘤组模型建立后第8天从尾静脉内注射2×106 USPIO-EPCs，分别在EPCs移植前、移植后1、3、5 d和7 d进行MRI扫描，观察病变区域在T2WI、SWI上信号和T2值的变化情况。在相对应时间点获取组织标本进行病理学分析，用普鲁士蓝染色检测有无阳性结果，并观察CD34+、SDF-1、MMP-9、VEGF等蛋白的表达以及与普鲁士蓝阳性细胞分布的关系。结果假肿瘤组在MRI上各时间点均无变化，T2值无明显变化，对照组肿瘤体积逐渐增大，但其内信号无明显变化，肿瘤组在移植USPIO-EPCs第1天后外周区在SWI上出现低信号，随着瘤龄的增长低信号逐渐增多并向肿瘤内部迁移，兴趣区T2值随时间逐渐下降。假肿瘤组普鲁士蓝染色见零星阳性细胞，肿瘤组移植USPIO-EPCs第1天见蓝染细胞主要分布于肿瘤外周区，之后逐渐向内迁移分布于肿瘤内部。同时，USPIO-EPCs移植后早期发现CD34+、SDF-1和MMP-9在肿瘤外周区表达较多，在USPIO-EPCs移植后第7天在肿瘤中央区域表达增多，且与肿瘤外周区并无明显差异，VEGF随着瘤龄的增长表达逐渐增多，但各时间点肿瘤中央区及肿瘤外周区表达无明显差异。结论MRI可以动态观察USPIO-EPCs在大鼠原位脑胶质瘤内归巢的变化过程，肿瘤组织不同区域SDF-1和MMP-9表达变化与USPIO标记的EPCs在肿瘤内的分布变化有相似性，这一发现表明SDF-1和MMP-9可能是促使移植的外源性EPCs由肿瘤周边向肿瘤中央区域迁移的分子生物学机制之一。
目的：探討超微型超順磁性氧化鐵粒子(USPIO)標記的外源性內皮祖細胞(EPCs)在大鼠腦原位膠質瘤內的動態歸巢特點，為利用磁性標記的EPCs作為MRI示蹤細胞載體提供可行性的實驗依據。材料與方法將SD大鼠分為假腫瘤組、腫瘤組和對照組3組，每組16隻，腫瘤組和對照組在腦組織內移植C6膠質瘤細胞，而假腫瘤組僅刺破腦組織不移植膠質瘤細胞。待腫瘤組和假腫瘤組模型建立後第8天從尾靜脈內註射2×106 USPIO-EPCs，分彆在EPCs移植前、移植後1、3、5 d和7 d進行MRI掃描，觀察病變區域在T2WI、SWI上信號和T2值的變化情況。在相對應時間點穫取組織標本進行病理學分析，用普魯士藍染色檢測有無暘性結果，併觀察CD34+、SDF-1、MMP-9、VEGF等蛋白的錶達以及與普魯士藍暘性細胞分佈的關繫。結果假腫瘤組在MRI上各時間點均無變化，T2值無明顯變化，對照組腫瘤體積逐漸增大，但其內信號無明顯變化，腫瘤組在移植USPIO-EPCs第1天後外週區在SWI上齣現低信號，隨著瘤齡的增長低信號逐漸增多併嚮腫瘤內部遷移，興趣區T2值隨時間逐漸下降。假腫瘤組普魯士藍染色見零星暘性細胞，腫瘤組移植USPIO-EPCs第1天見藍染細胞主要分佈于腫瘤外週區，之後逐漸嚮內遷移分佈于腫瘤內部。同時，USPIO-EPCs移植後早期髮現CD34+、SDF-1和MMP-9在腫瘤外週區錶達較多，在USPIO-EPCs移植後第7天在腫瘤中央區域錶達增多，且與腫瘤外週區併無明顯差異，VEGF隨著瘤齡的增長錶達逐漸增多，但各時間點腫瘤中央區及腫瘤外週區錶達無明顯差異。結論MRI可以動態觀察USPIO-EPCs在大鼠原位腦膠質瘤內歸巢的變化過程，腫瘤組織不同區域SDF-1和MMP-9錶達變化與USPIO標記的EPCs在腫瘤內的分佈變化有相似性，這一髮現錶明SDF-1和MMP-9可能是促使移植的外源性EPCs由腫瘤週邊嚮腫瘤中央區域遷移的分子生物學機製之一。
목적：탐토초미형초순자성양화철입자(USPIO)표기적외원성내피조세포(EPCs)재대서뇌원위효질류내적동태귀소특점，위이용자성표기적EPCs작위MRI시종세포재체제공가행성적실험의거。재료여방법장SD대서분위가종류조、종류조화대조조3조，매조16지，종류조화대조조재뇌조직내이식C6효질류세포，이가종류조부자파뇌조직불이식효질류세포。대종류조화가종류조모형건립후제8천종미정맥내주사2×106 USPIO-EPCs，분별재EPCs이식전、이식후1、3、5 d화7 d진행MRI소묘，관찰병변구역재T2WI、SWI상신호화T2치적변화정황。재상대응시간점획취조직표본진행병이학분석，용보로사람염색검측유무양성결과，병관찰CD34+、SDF-1、MMP-9、VEGF등단백적표체이급여보로사람양성세포분포적관계。결과가종류조재MRI상각시간점균무변화，T2치무명현변화，대조조종류체적축점증대，단기내신호무명현변화，종류조재이식USPIO-EPCs제1천후외주구재SWI상출현저신호，수착류령적증장저신호축점증다병향종류내부천이，흥취구T2치수시간축점하강。가종류조보로사람염색견령성양성세포，종류조이식USPIO-EPCs제1천견람염세포주요분포우종류외주구，지후축점향내천이분포우종류내부。동시，USPIO-EPCs이식후조기발현CD34+、SDF-1화MMP-9재종류외주구표체교다，재USPIO-EPCs이식후제7천재종류중앙구역표체증다，차여종류외주구병무명현차이，VEGF수착류령적증장표체축점증다，단각시간점종류중앙구급종류외주구표체무명현차이。결론MRI가이동태관찰USPIO-EPCs재대서원위뇌효질류내귀소적변화과정，종류조직불동구역SDF-1화MMP-9표체변화여USPIO표기적EPCs재종류내적분포변화유상사성，저일발현표명SDF-1화MMP-9가능시촉사이식적외원성EPCs유종류주변향종류중앙구역천이적분자생물학궤제지일。
Objective:The aim of this study was to investigate the dynamic homing characteristic of exogenous endothelial progenitor cells (EPCs) in rat glioma in vivo to provide an experimental basis for the feasibility of using magnetically labeled EPCs as MRI target tracing vectors. Materials and Methods:Three models of Sprague-Dawley at glioma (48 rats in total) were established as control group, experimental group and fake experimental group, In the control group and experimental group, orthotopic transplantation of C6 glioma cells was performed, compared to above groups, only the brain was punctured and no C6 glioma cells was performed. 8 days after the models were established, in the control group and experimental group, 2×106 USPIO-labeled EPCs were transplanted via the tail vein. Magnetic resonance imaging and perfusion-weighted imaging were performed on several days. The conventional MR imaging, including spin echo and gradin-echo sequence, were performed at before and 1, 3, 5, 7 days after transplantation on each group to observe the signal change of the diseased region on T2WI, SWI and T2 value. Tumors were excised from experimental rat of every group at each examined point to make pathological assay. Prussian blue staining represent the distribution of USPIO-EPCs in the tumor. CD34+, SDF-1, MMP-9 and VEGF staining were used to observe the distribution relationship between the Prussian blue staining positive cells and these antibody. Results:In fake experimental group, the MRI signal was similar all the time. The T2 value-time curve was straight. In control group, tumor size developed gradually but the no signal changed, in the experimental group, hypointense areas were detected at the periphery of the tumor on the ifrst day after transplantation of EPCs, and much more hypointense areas were observed inside the tumor over time. The T2 value-time curve was downtrending. There were a little blue-stained cells in fake experimental group, and several blue-stained cells were observed at the the periphery of the tumor on the ifrst day after transplantation of EPCs, and migrated in the center of the tumor gradually. At the sites of blued stained cells, both SDF-1 and MMP-9 were strongly positive, they showed generalized expression in the periphery of the tumor in the early stage, the number of positive antibodies gradually increased in the center of the tumor in the 7 day after transplantation of EPCs, conversely. There was no signiifcant association of blue stained cell localization and VEGF expression in tumor cells. Conclusions:The homing change procedure of USPIO-EPCs in rat glioma can observed by MRI in vivo, there was signiifcant correlation between USPIO-EPCs localization and the change of SDF-1 and MMP-9 in different areas, the antibody SDF-1 and MMP-9 may be one of the molecular biology of EPCs migration.
