用户名: 密码: 验证码:
大鼠C6脑胶质瘤3.0T MR-DTI及瘤周水肿浸润组织FA值与AQP1的相关性研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
第一部分Wistar大鼠C6脑胶质瘤模型的建立
     目的:建立稳定可靠的Wistar大鼠C6脑胶质瘤晚期阶段模型。
     材料和方法:1、C6细胞在含10%FBS、1%青链霉素混合液的RPMI-1640完全培养基中,置于37℃、5%CO2培养箱中培养,胰酶消化、终止,采集对数生长期的C6细胞计数,检测细胞活性,加完全培养基调整浓度。2、采用随机数字表将22只Wistar大鼠分成实验组17只,假手术组(对照组)5只。通过立体定向技术,将浓度大于1.0x106.10μ1的C6细胞接种至实验组大鼠右侧尾状核区,假手术组大鼠在相同部位注射完全培养基。3、肿瘤细胞接种后约3-4周对相应大鼠进行磁共振扫描和病理观察。
     结果:1、17只大鼠接种肿瘤细胞,1只死于术后约1h,1只于接种后15日不明原因死亡(随后病理证实有肿瘤形成),其余15只肿瘤细胞接种大鼠在随后的MRI和病理检查中均证实有肿瘤形成,接种成功率100%。假手术组5只大鼠均存活,且未见肿瘤形成。2、术后经磁共振及实验结束后的病理证实肿瘤细胞接种后约3-4周存在瘤周水肿和/或肿瘤细胞浸润。
     结论:Wistar大鼠C6脑胶质瘤模型稳定可靠,生长迅速,接种成功率高,肿瘤细胞接种后约3-4周,可满足瘤周水肿和/或肿瘤浸润实验要求。
     第二部分大鼠C6脑胶质瘤在体3.0T磁共振张量成像研究
     目的:探讨3.0T磁共振张量成像在Wistar大鼠C6胶质瘤肿瘤区和对侧正常脑实质区的各向异性分数(FA)值及平均弥散系数(MD)值,并比较两种不同的方法选取感兴趣区(ROI)对测量结果的影响。
     材料和方法:采用随机数字表将22只Wistar大鼠分成实验组17只,假手术组(对照组)5只。通过立体定向技术,将浓度大于1.0x106/10μ1的C6细胞接种至实验组大鼠右侧尾状核区,假手术组大鼠在相同部位注射完全培养基。肿瘤细胞接种后约3-4周,利用3.0T高场强医用磁共振扫描仪,大鼠专用线圈对大鼠C6胶质瘤模型行常规MRI、DT工、T1WI及SAG T1-3D-bravo增强检查,结合T2WI、FLAIR、T1WI及SAGT1-3D-bravo增强确定肿瘤与水肿区,借助Function Tool软件对DTI数据后处理,避开出血、坏死区,选取多个即3个等大(2mmm2,9pix)ROI和单个较大ROI,获得肿瘤实质和对侧正常脑实质区的FA及MD值。
     结果:15只成瘤大鼠中,肿瘤区和对侧正常脑实质区3个等大ROI FA平均值分别为(0.1075±0.02)和(0.312±0.024),而3个等大ROIMD值分别为(0.944±0.029)×10-3mm2/s和(0.808±0.036)×10-3mm2/s,两组结果经两样本t检验显示差别均有统计学意义(P<0.05)。肿瘤区和对侧正常脑实质区单个较大ROI FA平均值分为(0.118±0.039)和(0.310±0.052),而单个较大ROI MD平均值分别为(0.941±0.047)×10-3mm2/s和(0.806±0.043)×10-3mm2/s,两组结果经两样本t检验显示差别亦有统计学意义(P<0.05)。两种不同的方法选取肿瘤区ROI获得的FA值经配对t检验显示有统计学意义(P<0.05),而MD值间无统计学意义(P>0.05)。
     结论:用临床3.0T MRI行大鼠C6胶质瘤DTI检查切实可行,通过测量肿瘤区、对侧正常脑实质区FA及MD值,为以后的科研工作提供了有用的参考。方法学上,本研究发现两种不同的方法选取ROI对FA值测量结果有影响,而对MD值测量结果无明显影响。
     第三部分AQP1在鼠脑C6胶质瘤瘤周水肿浸润组织中的表达与FA值的相关性研究
     目的:研究Wistar大鼠C6脑胶质瘤瘤周水肿浸润组织的磁共振弥散张量成像(MR-DTI)的特征,并与免疫组织化学水通道蛋白1(AQP1)对照,探讨AQP1在胶质瘤瘤周水肿浸润组织中的表达与MR-DTI参数部分各向异性分数(FA)的相关性。
     材料与方法:采用随机数字表将22只Wistar大鼠分成实验组17只,假手术组(对照组)5只。通过立体定向技术,将浓度大于1.0×106/10ul的C6细胞接种至实验组大鼠右侧尾状核区,假手术组大鼠在相同部位注射完全培养基。肿瘤细胞接种后约3~4周,利用3.0T高场强医用磁共振扫描仪,大鼠专用线圈对大鼠C6胶质瘤模型行常规MRI、DTI、FLAIR、T1WI及SAG T1-3D-bravo增强检查,结合T2WI、FLAIR.T1WI及SAG T1-3D-bravo增强确定肿瘤与水肿区,借助Function Tool软件对DTI数据后处理,避开出血、坏死等影响结果的区域,选取多个即3个等大(2mm2,9pix)ROI,获得相应部位的FA值。设肿瘤对侧正常脑组织为内对照。MRI扫描完成后立即行4%的多聚甲醛灌注固定全脑,之后过量1%的戊巴比妥钠处死大鼠取全脑固定,选取与DTI肿瘤最大层面相对应的瘤周水肿区脑组织做连续冠状切片,进行HE染色和AQP1抗体免疫组织化学检查。Pearson相关分析法检测FA值和相应部位的AQPl阳性表达的IOD值的相关性,计算相关系数,并进行t检验,以P<0.05为有统计学意义。
     结果:15只成瘤大鼠中,瘤周水肿区约3-4周3个等大ROI FA平均值为(0.204±0.036),较对侧正常脑组织多个ROI FA平均值(0.310±0.027)降低,不过没有瘤体降低明显,两组结果经两样本t检验显示差别有统计学意义(P<0.05)。Pearson相关分析显示,肿瘤水肿浸润组织的FA值与AQP1阳性表达IOD值之间存在负相关(r=-0.81,P<0.05)。
     结论:Wistar大鼠C6脑胶质瘤瘤周水肿浸润组织MR-DTI参数FA值与AQP1之间存在负相关,随着AQP1阳性表达程度的增高,FA值降低。
Part I:The establishment of Wistar rat C6 brain glioma model
     Objective:To establish the stable and reliable late stage Wistar rat C6 brain glioma model.
     Materials and Methods:1.Rat C6 glioma cell lines were propagated in RPMI-1640 medium,supplemented with 10% fetal bovine serum,1% Penicillin-Streptomycin Solution,and were cultured with 5%C02 at 37℃in incubator. The tumor cells were maintained in continuous monolayer cell cultures in coming tissue culture flasks.Tumor cells were collected during logarithmic phase to count and detect cell activity.The concentrati-on were adjusted with complete medium.2.22 Wistar rats were divided into experimental group of 17 and control group of 5 by the random number table.The concentration of more than 1.0×106/10ul glioma cells and complete medium were injected stereotactically into the right caudate nucleus of the experimental group and control group, respectively.3. MRI scans and pathological observations were performed about 3~4 weeks after implantation for the rats.
     Results:1. One of the experimental group died after about lh,and another died of unknown causes 15 days afterr implantation (the pathology demonstrated tumor formation), the other 15 rats were confirmed the tumor formation by the subsequent MRI and pathological 硕士学位论文英文摘要examination.The control group of 5 were alive, and no tumor formation. 2. There is peritumor edema and/or tumor cell invasion about 3~4 weeks after implantation by Postoperative MRI and pathological examination.
     Conclusion:Wistar rat C6 glioma model is a stable and reliable model, After implantation,tumor grows rapidly,and the success rate is very high.The model can meet experimental requirements for the peritumoral edema and/or tumor infiltration about 3 to 4 weeks after inoculation.
     PartⅡ:The study of diffusion tensor imaging using 3.0T MR scanner in rat C6 brain glioma model in vivo
     Objective:To study the average fractional anisotropy(FA) and mean diffusivity (MD) values in the wistar rat C6 brain glioma regions and the contralateral normal brain parenchyma using 3.0T Magnetic resonance scanner,and compare the two different selective methods of region of interest (ROI).
     Materials and Methods:22 Wistar rats were divided into experim-ental group of 17 and control group of 5 by the random number table. The concentration of more than 1.0×106/10ul glioma cells and complete medium were stereotactically injected into the right caudate nucleus of the experimental group and controlgroup,respectively.Conventional MRI、DTI、enhanced T1WI and SAG T1-3D-bravo scans were performed using the GE Signa HDx 3.0T MRI scanner with the rat special coil about 3~4 weeks after implantation.And glioma and peritumoral edema were distin-guished by T2WI、FLAIR、enhanced T1WI and SAG T1-3D-bravo scans.Postproeessing was done by the DTI specific softw-are Function Tool to gain FA and MD images. ROIs were drawn,avoiding hemorrhage and necrosis areas, in different selective methods (3 equal-sized ROIs and a single larger ROI) in tumor parenchyma and the contralateral normal brain parenchyma.
     Results:The average FA values of 3 equal-sized ROIs in the 15 wistar rats C6 brain glioma regions and the contralateral normal brain parenchyma were (0.1075±0.02) and (0.312±0.024), respectively;the average MD values were (0.944±0.029)×10-3mm2/s and (0.808±0.036)×10-3mm2/s, respectively.Two independent-sample T test of the two groups showed statistically significant difference (P<0.05).The average FA values of single larger ROI in the wistar rat C6 brain glioma regions and the contralateral normal brain parenchyma were (0.118±0.039) and (0.310±0.052),respectively; the average MD values were(0.941±0.047)×10-3 mm2/s and (0.806±0.043)×10-3 mm2/s,respectively.Two independ-ent-sample T test of the two groups also showed statistically significant difference (P<0.05). Paired-sample T test of obtained FA values by the two different measurement methods showed statistically significant difference(P<0.05),while no statistical significance between the MD values (P> 0.05).
     Conclusion:It is feasible to perform DTI scan in the rat C6 brain glioma model using a clinical 3.0T MR scanner,and the FA and MD values measured in the rat C6 brain glioma regions and the contralateral normal brain parenchyma can be used for reference in future studies. Methodologically, the study showed the two different selective methods of region of interest could influence the measurements of FA vales, while have no effect on the measurements of MD values.
     Part III:The correlative study of AQP1 expression in rat brain glioma infiltrated peritumoral edema tissue and the FA value
     Objective:Magnetic resonance diffusion tensor imaging (MR-DTI) was performed in Wistar rat brain glioma infiltrated peritumoral edema tissue to analyze its features, and explore the correlation of AQP1 expression in rat brain glioma infiltrated peritumoral edema tissue by immunohistochemical findings and the FA value.
     Materials and Methods:22 Wistar rats were divided into experimental group of 17 and control group of 5 by the random number table.The concentration of more than 1.0×106/10ul glioma cells and complete medium were injected stereotactically into the right caudate nucleus of the experimental group and control group,respectively. Conv-entional MRI, DTI, enhanced T1WI and SAG T1-3D-bravo scans were performed using the GE Signa HDx 3.0T MRI scanner with the rat special coil about 3-4 weeks after implantation. And gliomas and peritumoral edema were distinguished by T2WI、FLAIR、enhanced T1WI and SAG T1-3D-bravo scans.Postproeessing was done using the DTI specific software Function Tool to gain FA images. ROIs were drawn, av-oiding hemorrhage and necrosis areas, in 3 equal-sized (2mm2,9pix). ROIs in peritumoral edema and the contralateral normal brain parenchy-ma to gain FA values. Let the contralateral normal brain tissue as an internal control. The whole rat brain was fixed by 4% paraformaldehyde perfusion after MRI scans immediately, and then the rats were sacrificed to take the whole brain fixed by excess of 1% sodium pentobarbital. Peritumoral brain edema tissue corresponding the maximum level of the tumor were selected to do continuous coronal sections. Each rat brain was examined histologically using HE and immunohistochemical staining for AQP1. Pearson correlation analysis was used to determine the relations between FA values and the IOD value of AQP1 expression.Correlation coefficient was also calculated and T test was made with statistical significance when P<0.05.
     Results:The average FA values of 3 equal-sized ROIs in the 15 rats C6 brain glioma peritumoral edema tissue about 3~4 weeks after implantation were (0.204±0.036). The results were lower than the average FA values (0.310±0.027) of the contralateral normal brain tissue. Two independent-sample T test of two groups showed statistically significant difference (P<0.05).Correlation were Negative between FA values of infiltrated peritumoral edema tissue and the IOD value of AQP1 expression(r=-0.81,P<0.05).
     Conclusion:The correlation of AQP1 expression in rat brain glioma infiltrated peritumoral edema tissue and the FA value were negative.with the increase of AQP1 expression level, FA value decreased.
引文
[1]San-Galli F, Vrignaud P, Robert J, et al. Assessment of the experimental model of transplanted C6 glioblastoma in Wistar rats. J Neurooncol,1989,7(3): 299-304
    [2]Chicoine MR, Silbergeld DL. Invading C6 glioma cells maintaining tumorigenicity. J Neurosurg,1995,83(4):665-671
    [3]Badie B, Hunt K, Economou JS, et al. Stereotactic delivery of a recombinant adenovirus into a C6 glioma cell line in a rat brain tumor model. Neurosurgery, 1994,35(5):910-916
    [4]Asanuma T, Doblas S, Tesiram YA, et al. Visualization of the protective ability of a free radical trapping compound against rat C6 and F98 gliomas with diffusion tensor fiber tractography. J Magn Reson Imaging,2008,28(3): 574-587
    [5]姬西团,赵明,王西玲,等.脑胶质瘤动物的模型建立及cyclin D1表达的观察.第四军医大学学报,2003,(22):2021-2023
    [6]李明,李飞,吴南,等.大鼠C6脑胶质瘤模型的病理特征与MRI的观察.中华神经外科杂志,2005,(05):279-282
    [7]Paxinos G,Watson C.The Rat Brainin Stereotaxic Coordinates, compact third edition.California:Academic Press, Inc,1997.8-90
    [8]邱大胜,徐丽莹,尹明媛,等.注射后留置时间对大鼠C6脑胶质瘤模型的影响.重庆医科大学学报,2008,(10):1260-1263
    [9]Oka N, Soeda A, Inagaki A, et al. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells. Biochem Biophys Res Commun,2007,360(3):553-559
    [10]吴国祥,李承晏,喻文莉.鼠脑胶质瘤模型的建立.卒中与神经疾病,2000,(04):218-220
    [11]Grobben B, De Deyn PP, Slegers H. Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion. Cell Tissue Res, 2002,310(3):257-270
    [12]李维方,朱诚,王金林.立体定向大鼠C_6脑胶质瘤动物模型的建立.立体定向和功能性神经外科杂志,2000,(02):63-66
    [13]dos SER, Daval J, Koziel V, et al. Toxic effects of apomorphine on rat cultured neurons and glial C6 cells, and protection with antioxidants. Biochem Pharmacol,2001,61(1):73-85
    [14]Barth RF. Rat brain tumor models in experimental neuro-oncology:the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas. J Neurooncol,1998,36(1): 91-102
    [15]吴波,黄光富,游潮,等.C6脑胶质瘤血-瘤屏障通透性与超微结构研究.中华实验外科杂志,2007,(09):1052-1054
    [16]张清波.MR灌注成像对大鼠脑C6胶质瘤血管生成的实验研究:[博士学位论文].上海:复旦大学,2006
    [17]章翔,李侠,吴景文,等.脑胶质细胞瘤体内侵袭性的实验研究.中华医学杂志,2001,81(3):150-153
    [18]余永强,钱银锋,张玲玲.立体定向建立大鼠C6脑胶质瘤模型.中国药理学通报,2003,(02):222-225
    [19]范国光,臧培卓,景奉东,等.大鼠C6脑胶质瘤MR扩散加权成像及灌注成像与组织学对照研究.中华放射学杂志,2005,39(6):613-618
    [1]Mayer D, Zahr NM, Adalsteinsson E, et al. In vivo fiber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil. Neuroimage,2007,35(3):1077-1085
    [2]Baratti C, Barnett AS, Pierpaoli C. Comparative MR imaging study of brain maturation in kittens with T1, T2, and the trace of the diffusion tensor. Radiology, 1999,210(1):133-142
    [3]Yuan W, Deren KE,2nd MJP, et al. Diffusion tensor imaging correlates with cytopathology in a rat model of neonatal hydrocephalus. Cerebrospinal Fluid Res, 2010,7:19
    [4]Asanuma T, Doblas S, Tesiram YA, et al. Visualization of the protective ability of a free radical trapping compound against rat C6 and F98 gliomas with diffusion tensor fiber tractography. J Magn Reson Imaging,2008,28(3):574-587
    [5]Lope-Piedrafita S, Garcia-Martin ML, Galons JP, et al. Longitudinal diffusion tensor imaging in a rat brain glioma model. NMR Biomed,2008,21(8):799-808
    [6]陶晓峰,施增儒,肖湘生,等.鼠脑胶质瘤模型的建立与增强磁共振成像研究.中国医学计算机成像杂志,1999,(3):204-207
    [7]Wang W, Steward CE, Desmond PM. Diffusion tensor imaging in glioblastoma multiforme and brain metastases:the role of p, q, L, and fractional anisotropy. AJNR Am J Neuroradiol,2009,30(1):203-208
    [8]杜渭清.磁共振灌注成像在脑胶质瘤的临床应用及动物实验研究:[博士学位论文].西安:第四军医大学,2004
    [9]张清波.MR灌注成像对大鼠脑C6胶质瘤血管生成的实验研究:[博士学位论文].上海:复旦大学,2006
    [10]吴波,黄光富,游潮,等.C6脑胶质瘤血-瘤屏障通透性与超微结构研究.中华实验外科杂志,2007,(9):1052-1054
    [11]Basser PJ, Pierpaoli C. Micro structural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B,1996,111(3): 209-219
    [12]Basser PJ. New histological and physiological stains derived from diffusion-tensor MR images. Ann N Y Acad Sci,1997,820:123-138
    [13]Pierpaoli C, Jezzard P, Basser PJ, et al. Di CG. Diffusion tensor MR imaging of the human brain. Radiology,1996,201(3):637-648
    [14]Wakana S, Jiang H, Nagae-Poetscher LM, et al. Fiber tract-based atlas of human white matter anatomy. Radiology,2004,230(1):77-87
    [15]Skare S, Hedehus M, Moseley ME, et al. Condition number as a measure of noise performance of diffusion tensor data acquisition schemes with MRI. J Magn Reson,2000,147(2):340-352
    [16]Abe O, Aoki S, Hayashi N, et al. Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis. Neurobiol Aging,2002,23(3): 433-441
    [17]Kinoshita M, Hashimoto N, Goto T, et al. Fractional anisotropy and tumor cell density of the tumor core show positive correlation in diffusion tensor magnetic resonance imaging of malignant brain tumors. Neuroimage,2008,43(1):29-35
    [18]Stadlbauer A, Ganslandt O, Buslei R, et al. Gliomas:histopathologic evaluation of changes in directionality and magnitude of water diffusion at diffusion-tensor MR imaging. Radiology,2006,240(3):803-810
    [19]Beppu T, Inoue T, Shibata Y, et al. Measurement of fractional anisotropy using diffusion tensor MRI in supratentorial astrocytic tumors. J Neurooncol,2003, 63(2):109-116
    [20]刘影,李传福,张凯,等.星形细胞瘤各向异性分数值与其内部微结构的相关性分析.中华放射学杂志,2007,41(4):355-357
    [21]Asanuma T, Doblas S, Tesiram YA, et al. Diffusion tensor imaging and fiber tractography of C6 rat glioma. J Magn Reson Imaging,2008,28(3):566-573
    [22]Lu S, Ahn D, Johnson G, et al. Diffusion-tensor MR imaging of intracranial neoplasia and associated peritumoral edema:introduction of the tumor infiltration index. Radiology,2004,232(1):221-228
    [23]Provenzale JM, McGraw P, Mhatre P, et al. Peritumoral brain regions in gliomas and meningiomas:investigation with isotropic diffusion-weighted MR imaging and diffusion-tensor MR imaging. Radiology,2004,232(2):451-460
    [1]Kelly PJ, Daumas-Duport C, Kispert DB, et al. Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. J Neurosurg,1987, 66(6):865-874
    [2]Laws ER Jr, Shaffrey ME. The inherent invasiveness of cerebral gliomas: implications for clinical management. Int J Dev Neurosci,1999,17(5-6): 413-420
    [3]Lu S, Ahn D, Johnson G, et al. Peritumoral diffusion tensor imaging of high-grade gliomas and metastatic brain tumors. AJNR Am J Neuroradiol, 2003,24(5):937-941
    [4]Lu S, Ahn D, Johnson G, et al. Diffusion-tensor MR imaging of intracranial neoplasia and associated peritumoral edema:introduction of the tumor infiltration index. Radiology,2004,232(1):221-228
    [5]Deng Z, Yan Y, Zhong D, et al. Quantitative analysis of glioma cell invasion by diffusion tensor imaging. J Clin Neurosci,2010,17(12):1530-1536
    [6]Mori S, Frederiksen K, van ZPC, et al. Brain white matter anatomy of tumor patients evaluated with diffusion tensor imaging. Ann Neurol,2002,51(3): 377-380
    [7]Yamada K, Kizu O, Mori S, et al. Brain fiber tracking with clinically feasible diffusion-tensor MR imaging:initial experience. Radiology,2003,227(1): 295-301
    [8]Provenzale JM, McGraw P, Mhatre P, et al. Peritumoral brain regions in gliomas and meningiomas:investigation with isotropic diffusion-weighted MR imaging and diffusion-tensor MR imaging. Radiology,2004,232(2):451-460
    [9]Price SJ, Pena A, Burnet NG, et al. Detecting glioma invasion of the corpus callosum using diffusion tensor imaging. Br J Neurosurg,2004,18(4):391-395
    [10]Splinter PL, Masyuk Al, LaRusso NF. Specific inhibition of AQP1 water channels in isolated rat intrahepatic bile duct units by small interfering RNAs. J Biol Chem,2003,278(8):6268-6274
    [11]Deen PM, Weghuis DO, Geurs vKA, et al. The human gene for water channel aquaporin 1 (AQP1) is localized on chromosome 7p15-->pl4. Cytogenet Cell Genet,1994,65(4):243-246
    [12]Nakano I, Kondo A, Iwasaki K. Choroid plexus papilloma in the posterior third ventricle:case report. Neurosurgery,1997,40(6):1279-1282
    [13]孟辉,刘国龙,唐荣锐,等.大鼠实验性脑室出血后水通道蛋白1在脑内的表达及意义.中华神经医学杂志,2010,9(1):11-14,19
    [14]杨志亮.托吡酯对硝酸甘油致大鼠偏头痛模型血浆和脑组织中水通道蛋白1表达的影响:[硕士学位论文].沈阳:中国医科大学,2010
    [15]Oshio K, Binder DK, Liang Y, et al. Expression of the aquaporin-1 water channel in human glial tumors. Neurosurgery,2005,56(2):375-381
    [16]Endo M, Jain RK, Witwer B, et al. Water channel (aquaporin 1) expression and distribution in mammary carcinomas and glioblastomas. Microvasc Res, 1999,58(2):89-98
    [17]Kobayashi H, Yokoo H, Yanagita T, et al. Induction of aquaporin 1 by dexamethasone in lipid rafts in immortalized brain microvascular endothelial cells. Brain Res,2006,1123(1):12-19
    [18]Monzani E, Bazzotti R, Perego C, et al. AQP1 is not only a water channel:it contributes to cell migration through Lin7/beta-catenin. PLoS One,2009,4(7): e6167
    [19]高晓葳,黄永旺,刘静.水通道蛋白1和血管内皮生长因子在喉鳞状细胞癌组织中的表达及相关性研究.临床耳鼻咽喉头颈外科杂志,2009,(9):407-410
    [20]Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev,2005,15(1):102-111
    [21]Hashizume H, Baluk P, Morikawa S, et al. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol,2000,156(4): 1363-1380
    [22]Papadopoulos MC, Saadoun S, Verkman AS. Aquaporins and cell migration. Pflugers Arch,2008,456(4):693-700
    [23]Liang HT, Feng XC, Ma TH. Water channel activity of plasma membrane affects chondrocyte migration and adhesion. Clin Exp Pharmacol Physiol, 2008,35(1):7-10
    [24]McCoy E, Sontheimer H. Expression and function of water channels (aquaporins) in migrating malignant astrocytes. Glia,2007,55(10):1034-1043
    [25]Verkman AS, Hara-Chikuma M, Papadopoulos MC. Aquaporins--new players in cancer biology. J Mol Med,2008,86(5):523-529
    [26]Oshio K, Binder DK, Bollen A, et al. Aquaporin-1 expression in human glial tumors suggests a potential novel therapeutic target for tumor-associated edema. Acta Neurochir Suppl,2003,86:499-502
    [27]陆华东.水通道蛋白在非小细胞肺癌中的表达及其意义:[硕士学位论文].温州:温州医学院,2009
    [28]Wang W, Steward CE, Desmond PM. Diffusion tensor imaging in glioblastoma multiforme and brain metastases:the role of p, q, L, and fractional anisotropy. AJNR Am J Neuroradiol,2009,30(1):203-208
    [29]Werring DJ, Toosy AT, Clark CA, et al. Diffusion tensor imaging can detect and quantify corticospinal tract degeneration after stroke. J Neurol Neurosurg Psychiatry.2000,69(2):269-272
    [30]Le BD, Mangin JF, Poupon C, et al. Diffusion tensor imaging:concepts and applications. J Magn Reson Imaging,2001,13(4):534-546
    [31]Lope-Piedrafita S, Garcia-Martin ML, Galons JP, et al. Longitudinal diffusion tensor imaging in a rat brain glioma model. NMR Biomed,2008,21(8): 799-808
    [32]Stieltjes B, Schluter M, Didinger B, et al. Diffusion tensor imaging in primary brain tumors:reproducible quantitative analysis of corpus callosum infiltration and contralateral involvement using a probabilistic mixture model. Neuro-image,2006,31(2):531-542
    [33]Pierpaoli C, Jezzard P, Basser PJ, et al. Diffusion tensor MR imaging of the human brain. Radiology,1996,201(3):637-648
    [34]Wakana S, Jiang H, Nagae-Poetscher LM, et al. Fiber tract-based atlas of human white matter anatomy. Radiology,2004,230(1):77-87
    [35]Skare S, Hedehus M, Moseley ME, et al. Condition number as a measure of noise performance of diffusion tensor data acquisition schemes with MRI. J Magn Reson,2000,147(2):340-352
    [36]张冬,廖翠薇,舒通胜,等.脑胶质瘤的磁共振弥散张量成像研究.第三军医大学学报,2008,30(16):1496-1498
    [37]晏怡,邓朝霞,唐文渊,等.胶质瘤脑浸润程度与病理级别的相关性研究.中华神经外科疾病研究杂志,2010,9(4):332-336
    [38]Wang S, Kim S, Chawla S, et al. Differentiation between glioblastomas and solitary brain metastases using diffusion tensor imaging. Neuroimage,2009, 44(3):653-660
    [39]Wang S, Kim S, Chawla S, et al. Differentiation between Glioblastomas, Solitary Brain Metastases, and Primary Cerebral Lymphomas Using Diffusion Tensor and Dynamic Susceptibility Contrast-Enhanced MR Imaging. AJNR Am J Neuroradiol,2011,32(3):507-514
    [40]刘影.DTI在颅内肿瘤中的应用以及肿瘤FA与其微结构特点的相关性研究:[博士学位论文].济南:山东大学,2005
    [41]鲁宏,胡惠,杨娜,等.水通道蛋白-4在大鼠急性脑缺血再灌注脑组织中的表达.解剖学杂志,2008,31(1):47-50,59
    [42]鲁宏,章士正,胡惠,等.大鼠脑缺血再灌注的MR扩散加权成像与水通道蛋白-4表达的相关性研究.中华放射学杂志,2009,43(12):1319-1321
    [1]Pavlisa G, Rados M, Pavlisa G,et al. The differences of water diffusion between brain tissue infiltrated by tumor and peritumoral vasogenic edema. Clin Imaging,2009,33(2):96-101
    [2]Pronin IN, Holodny AI, Petraikin AV. MRI of high-grade glial tumors: correlation between the degree of contrast enhancement and the volume of surrounding edema. Neuroradiology,1997,39(5):348-350
    [3]Law M, Cha S, Knopp EA,et al. High-grade gliomas and solitary metastases: differentiation by using perfusion and proton spectroscopic MR imaging. Radiology,2002,222(3):715-721
    [4]Dickinson PJ, Sturges BK, Higgins RJ, et al. Vascular endothelial growth factor mRNA expression and peritumoral edema in canine primary central nervous system tumors. Vet Pathol,2008,45(2):131-139
    [5]Papadopoulos MC, Saadoun S, Verkman AS. Aquaporins and cell migration. Pflugers Arch,2008,456(4):693-700
    [6]Otsuka S, Tamiya T, Ono Y, et al. The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas. J Neurooncol,2004,70(3):349-357
    [7]Miles KA. Measurement of tissue perfusion by dynamic computed tomography. Br J Radiol,1991,64(761):409-412
    [8]Inao S, Kuchiwaki H, Ichimi K, et al. Assessment of vasoreactivity in brain edema by acetazolamide activation SPECT and PET. Acta Neurochir Suppl,1997,70:165-166
    [9]Chiang IC, Kuo YT, Lu CY, et al. Distinction between high-grade gliomas and solitary metastases using peritumoral 3-T magnetic resonance spectroscopy, diffusion, and perfusion imagings. Neuroradiology,2004,46(8):619-627
    [10]Weber MA, Zoubaa S, Schlieter M, et al. Diagnostic performance of spectroscopic and perfusion MRI for distinction of brain tumors. Neurology, 2006,66(12):1899-1906
    [11]Sergides I, Hussain Z, Naik S,et al. Utilization of dynamic CT perfusion in the study of intracranial meningiomas and their surrounding tissue. Neurol Res,2009,31(1):84-89
    [12]Kapoor GS, Gocke TA, Chawla S, et al. Magnetic resonance perfusion-weighted imaging defines angiogenic subtypes of oligodendroglioma according to 1p19q and EGFR status. J Neurooncol,2009,92(3):373-386
    [13]Veeravagu A, Hou LC, Hsu AR, et al. The temporal correlation of dynamic contrast-enhanced magnetic resonance imaging with tumor angiogenesis in a murine glioblastoma model. Neurol Res,2008,30(9):952-959
    [14]丁蓓,凌华威,张欢,等.胶质瘤CT灌注成像对脑血容量与血管表面通透性的相关性研究.中华放射学杂志,2007,41(1):25-28
    [15]王志群,李坤成,王亮,等.磁共振波谱成像对颅脑肿瘤的鉴别诊断价值.放射学实践,2007,22(2):132-135
    [16]Sibtain NA, Howe FA, Saunders DE. The clinical value of proton magnetic resonance spectroscopy in adult brain tumours. Clin Radiol,2007,62(2):109-119
    [17]Ricci R, Bacci A, Tugnoli V, et al. Metabolic findings on 3T 1H-MR spectroscopy in peritumoral brain edema. AJNR,2007,28(7):1287-1291
    [18]姜涛,张竞文,伍建林,等.磁共振氢质子波谱对脑肿瘤瘤周水肿的临床应用研究.中国医学计算机成像杂志,2006,12(1):11-15
    [19]Cruz Junior LC, Sorensen AG. Diffusion tensor magnetic resonance imaging of brain tumors. Neurosurg Clin N Am,2005,16(1):115-134
    [20]Provenzale JM, McGraw P, Mhatre P,et al. Peritumoral brain regions in gliomas and meningiomas:investigation with isotropic diffusion-weighted MR imaging and diffusion-tensor MR imaging. Radiology,2004,232(2):451-460
    [21]Wang S, Kim S, Chawla S, et al. Differentiation between glioblastomas and solitary brain metastases using diffusion tensor imaging. Neuroimage,2009, 44(3):653-660
    [22]晏怡,唐文渊,邓朝霞,等.弥散张量成像(DTI)对肿瘤脑浸润的量化和应用.中国神经精神疾病杂志,2008,34(11):666-670
    [23]麦筱莉,储成凤,秦伟,等.多体素1H-MRS和DWI对脑肿瘤强化周边区的评价.中国医学影像技术,2006,22(4):513-517
    [24]Kono K, Inoue Y, Nakayama K, et al. The role of diffusion-weighted imaging in patients with brain tumors. AJNR,2001,22(6):1081-1088
    [25]吴静,戴建平,江涛,等.多形性胶质母细胞瘤MR弥散张量成像应用研究.中国医学影像技术,2008,24(07):992-995
    [26]Castillo M, Smith JK, Kwock L, et al. Apparent diffusion coefficients in the evaluation of high-grade cerebral gliomas. AJNR,2001,22(1):60-64
    [27]Sinha S;Bastin ME; Whittle IR, et al. Diffusion tensor MR imaging of high-grade cerebral gliomas.AJNR,2002,23(4):520-527
    [28]Cenic A, Nabavi DG, Craen RA,et al. A CT method to measure hemodynamics in brain tumors:validation and application of cerebral blood flow maps. AJNR, 2000,21 (3):462-470
    [29]Barajas RF Jr, Chang JS, Segal MR, et al. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology,2009,253(2):486-496
    [30]Verma R, Zacharaki El, Ou Y, et al. Multiparametric tissue characterization of brain neoplasms and their recurrence using pattern classification of MR images. Acad Radiol,2008,15(8):966-977
    [1]Splinter PL, Masyuk AI, LaRusso NF. Specific inhibition of AQP1 water chann-els in isolated rat intrahepatic bile duct units by small interfering RNAs. J Biol Chem,2003,278(8):6268-6274
    [2]Monzani E, Bazzotti R, Perego C,et al. AQP1 is not only a water channel:it contributes to cell migration through Lin7/beta-catenin. PLoS One,2009,4(7) :e6167
    [3]Papadopoulos MC, Saadoun S, Verkman AS. Aquaporins and cell migration. Pflugers Arch,2008,456(4):693-700
    [4]Deen PM, Weghuis DO, Geurs van Kessel A,et al. The human gene for water channel aquaporin 1 (AQP1) is localized on chromosome 7p15->p14. Cytogenet Cell Genet,1994,65(4):243-246
    [5]King LS, Agre P. Pathophysiology of the aquaporin water channels. Annu Rev Physiol,1996,58:619-648
    [6]路杨,袁芳.水通道蛋白1与脑肿瘤.中国微侵袭神经外科杂志,2008,13(12):574-576
    [7]Gomori E, Pal J, Abraham H,et al. Fetal development of membrane water channel proteins aquaporin-1 and aquaporin-4 in the human brain. Int J Dev Neurosci,2006,24(5):295-305
    [8]Kobayashi H, Yanagita T, Yokoo H,et al. Molecular mechanisms and drug development in aquaporin water channel diseases:aquaporins in the brain. J Pharmacol Sci,2004,96(3):264-270
    [9]安宇,张剑钊,李学军.水通道蛋白的表达及其调节.国际药学研究杂志,2008,35(5):355-359
    [10]吴琴琴,陈玉成,姜小飞,等.缺氧条件下体外培养血管内皮细胞AQP1表达的变化.四川大学学报,2008,39(6):916-920
    [11]King LS, Nielsen S, Agre P. Aquaporin-1 water channel protein in lung: ontogeny, steroid-induced expression, and distribution in rat. J Clin Invest, 1996,97(10):2183-2191
    [12]Stoenoiu MS, Ni J, Verkaeren C,et al. Corticosteroids induce expression of aquaporin-1 and increase transcellular water transport in rat peritoneum. J Am Soc Nephrol,2003,14(3):555-565
    [13]Umenishi F, Schrier RW. Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene. J Biol Chem,2003,278(18):15765-15770
    [14]Johansson P, Dziegielewska K, Saunders N. Low levels of Na, K-ATPase and carbonic anhydrase Ⅱ during choroid plexus development suggest limited involvement in early CSF secretion. Neurosci Lett,2008,442(1):77-80
    [15]Zhang W, Zitron E, Homme M,et al. Aquaporin-1 channel function is positively regulated by protein kinase C. J Biol Chem,2007,282(29):20933-20940
    [16]Kaneko K, Yagui K, Tanaka A,et al. Aquaporin 1 is required for hypoxia-indu-cible angiogenesis in human retinal vascular endothelial cells. Microvasc Res, 2008,75(3):297-301
    [17]孟肖利,陈劲草,王正峰,等.AQP-1和VEGF在星形细胞瘤中的表达及其意义.中国临床神经外科杂志,2007,12(5):276-277,287
    [18]Oshio K, Binder DK, Liang Y,et al. Expression of the aquaporin-1 water channel in human glial tumors. Neurosurgery,2005,56(2):375-381
    [19]索新,郭永川,郭宏川.水通道蛋白1基因在人脑胶质瘤中的表达及意义.中国微侵袭神经外科杂志,2003,8(6):270-272
    [20]Markert JM, Fuller CM, Gillespie GY,et al. Differential gene expression profiling in human brain tumors. Physiol Genomics,2001,5(1):21-33
    [21]高晓葳,黄永旺,刘静.水通道蛋白1和血管内皮生长因子在喉鳞状细胞癌组织中的表达及相关性研究.临床耳鼻咽喉头颈外科杂志,2009,23(9):407-410
    [22]Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev,2005,15(1):102-111
    [23]Hashizume H, Baluk P, Morikawa S,et al. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol,2000, 156(4):1363-1380
    [24]Liang HT, Feng XC, Ma TH. Water channel activity of plasma membrane affects chondrocyte migration and adhesion. Clin Exp Pharmacol Physiol, 2008,35(1):7-10
    [25]Hu J, Verkman AS. Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. FASEB J,2006,20(11):1892-1894
    [26]McCoy E, Sontheimer H. Expression and function of water channels (aquaporins) in migrating malignant astrocytes[J]. Glia,2007, 55:1034-1043.
    [27]鲁宏,熊仁平,胡惠,等.水通道蛋白-4在脑缺血半暗带组织中的表达.中华放射学杂志,2005,39(6):604-607.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700