摘要
第一部分应用HR-MRI对正常眼眼外肌、泪腺、眼球容积生物测量的研究
目的应用HR-MRI技术对正常人眼部结构进行活体生物测量,获取在活体状态下眼部组织结构形态及其精确数值,建立正常眼活体组织测量值,为眼科研究、教学及临床诊断提供理论数据。
方法选择正常志愿者100例(200眼眶),其中男性50例(100眼眶),女性50例(100眼眶),所有受试者均行HR-MRI眼眶扫描,并应用图像处理软件进行相关参数测量分析:1、眼外肌肌腹最大径层面的水平径及垂直径。2、眼眶直肌坐标值及眼球动态直肌横截面积。3、泪腺MRI表现及测量。4、眼球容积。
结果1、正常国人两侧眼外肌对称,且粗细有一定的规律,最大径线层面内各条眼外肌短径大小关系:下直肌>内直肌>上直肌>外直肌;长径大小关系:外直肌>内直肌>上直肌>下直肌。2、(1)原在位时,相对于眼眶中心的坐标值分别为内直肌(12.53mm,-2.25mm);外直肌(-14.35mm,-2.86mm);上直肌(1.9mm,12.00mm);下直肌(4.80mm,-11.40mm);(2)原在位及4条直肌收缩和松弛时,在MRI图像上直肌最大横截面积所在层面位于眼球-视神经连接平面后6mm处;(3)直肌收缩和松弛时,MRI图像上横截面积变化幅度由大到小依次为上直肌、下直肌、内直肌、外直肌。3、在T2WI上85例泪腺与脑白质信号相近,15例泪腺信号略高;在T1WI上泪腺与脑白质信号相近;在T1WI脂肪抑制序列,泪腺呈高信号;男性泪腺面积左、右两侧间无明显差异,女性泪腺面积左、右两侧间有显著差异,右侧略大,泪腺面积无明显性别间差异;男性眶缘前部泪腺面积比率(Sr)值左、右两侧间无明显差异,女性Sr值左、右两侧间有显著差异,左侧大于右侧;男、女性的Sr值均随年龄增加而增大,Sr值无明显性别间差异。4、所测的容积值:玻璃体腔容积4.514±0.323cm3,与“眼科测量正常值”比较,差异无统计学意义(P=0.148)。球内总容积、眼房水容积、晶状体容积分别为5.146±0.352cm3.0.244±0.385cm3、0.223±0.222cm3,与“眼科测量正常值”比较,差异有统计学意义(P<0.001)。
结论1、判断眼外肌大小是否正常可利用双侧眼外肌对称性及眼外肌粗细规律来判断。2、正常人原在位MRI图像4条直肌横截面中心在眼眶内坐标值及4条直肌收缩和松弛时横截面积变化的正常比值的建立,为眼外肌病的MRI诊断及手术治疗提供了参考。3、MRI横断面及冠状面均可以清楚显示泪腺,非增强T1WI脂肪抑制序列可较好地显示泪腺的形态、结构、位置及与邻近结构的关系;双侧泪腺的大小、形态并不完全对称;随着年龄的增长,泪腺可有向前、下、外方的移位;泪腺大小、位置无明显性别间差异。4、MRI可较好的应用于活体眼球容积的测量。所测玻璃体腔容积与“眼科测量正常值”之间差异不显著;球内总容积小于“眼科测量正常值”;眼前房及晶状体稍大于“眼科测量正常值”。
第二部分不同年龄正常眼眶容积的MRI测量
目的探讨正常眼眶容积的发育规律,建立中国人群眼眶容积磁共振扫描(MRI)测量的正常参考值。
方法选择100例眼部无阳性病征,男性50例、女性50例,根据年龄分组,应用磁共振扫描技术,在眼眶的横断、冠状及平行视神经的斜矢状位扫描,计算眼眶容积,分析眼眶容积与年龄、性别的关系。
结果眼眶容积在各年龄阶段左右对称,20岁之前眼眶容积增长迅速,大约男性17岁、女性13岁时平均眼眶容积分别为25.59ml、23.64m1,达正常成年人眶容积的95%,正常成人眼眶容积男性大于女性,男女性平均眼眶容积分别为27.22±3.27ml、24.88±3.04ml。眼眶容积与年龄呈显著正相关(P<0.05),但14岁之前男女性眼眶容积比较差异无统计学意义(P>0.05)。
结论正常人眼眶容积左右对称,其大小与年龄、性别有关,且20岁之前增长迅速,40岁之后仍缓慢增长。
Part Ⅰ Study on normal ophthalmic tissues among EONs、lacrimal gland and ocular volume structure measurement by High-Resolution MRI
Objective The HR-magnetic resonance imaging (MRI) technology was applied to measure the ocular structures of healthy people in order to establish database for ocular structures and provide theoretical support for eye research, teaching and diagnosis.
Methods Choose100cases of normal volunteers (200orbits),50cases of male (100orbits),50cases of female orbital (100orbits), all the subjects accepted line HR-orbital MRI, and image processing software was applied to morphology and statistical analysis.1. Measurement of extraocular muscle, muscle belly level horizontal diameter and maximum diameter vertical diameter.2. Eye rectus coordinates, and eye dynamic rectus muscle cross-sectional area.3. The MRI manifestation of lacrimal gland and measurement.4. Eye volume measurement
Results l.The EOMs of normal Chinese were symmetrical on the two sides, and following a certain rule. The relationships of the short diameters of EOMs in the Maximum Planes were:IR>MR>SR>LR. That of the long diameters of EOMs were: IR>MR>SR>IR.2.(1) In the primary position, on the plane of eye-optic nerve cross, the coordination of the medial rectus, lateral rectus, superior rectus and inferior rectus muscle relative to the orbital center are (12.53mm,-2.25mm),(-14.35mm,-2.86mm),(1.90mm,12.00mm),(4.80mm,-11.40mm);(2) In the primary position, left, right, up, down gaze, the largest cross-section of the rectus muscles is on the plane of6mm posterior to the plane of eye-optic nerve cross on the images of coronal MRI scan;(3) When the rectus contact and relax, the most obvious change of cross-section is the superior rectus muscle, followed by the inferior rectus, the medial rectus and the lateral rectus muscle, respectively.3.On T2WI the lacrimal gland showed isointensity signal in85and hyperintensity signal in15subjects with respect to the cerebral white matter. On T1WI, the lacrimal gland showed isointensity signal. OnT1WI+FS, the lacrimal gland showed hyperintensity signal. There was no significant difference in the area of the lacrimal gland between sides in men. But in women, the area of the right lacrimal gland was larger than that of left lacrimal. No significant difference was observed in the area of the lacrimal gland between the men and women. There was no significant difference in the Sr of the lacrimal gland between sides in men. But in women, the Sr of the left side lacrimal gland was larger than that of right side. The Sr showed an age-related increase in both men and women.4. The volume of the vitreous cavity4.514±0.323cm3was little different from the anatomic normal value(P=0.148); The volumes of the ocular globe, the anterior chamber, and the lens cavity were5.146±0.352cm3,0.244±0.385cm3,0.223±0.222cm3, with no statistic differences compared with those of the anatomic normal values.
Conclusions1.Sizes of EOMs can be assessed by the symmetry on the two sides and by observing the usual rule of EOMs2.We established the rectus muscle coordination of the normal Chinese on the image of coronal orbit MRI and the rate of the cross-section change when the rectus contract and relax in this study, which may help us to diagnose and treat the strabismus.3. Both axial and coronal planes of MR imaging could demonstrate clearly the lacrimal gland. The intensity of the lacrimal gland was similar to the cerebral white matter. Non-enhanced T1WI+FS sequence could show the configuration structure、location and adjacent tissues of the lacrimal gland clearly. Bilateral lacrimal glands were not symmetrical exactly. Lacrimal gland may have anterior、inferior and lateral displacement with age increased.4. MRI could be used for measuring ocular volume. Compared with the anatomic normal value, there was no significant difference in the vitreous cavity volume although the volumes of the lens and the anterior chamber seemed a little bigger.
Part Ⅱ Study on the growth of orbital volume in individuals at different ages by MRI
Objective To study the growth aspects of orbital volume and to establish the normal value of orbital volume by magnetic resonance imaging (MRI).
Method One hundred individuals without eye diseases (50males,50females) were divided into5groups according to the age. Orbital volume and length of horizontal transverse axis and anterior-posterior axis of the eye were measured at different age in MRI. The relationship between orbital volume and age, gender was analyzed.
Results There was no difference between the left and right orbital volume in all age groups. Orbital volume grew rapidly before20years of old. Mean orbital volume inmales aged17and females aged13was25.59and23.64ml, respectively, which reached95%of the adult orbital volume. In normal adult, orbital volume in the male was larger than that of the female. The mean orbital volume of adult male and female was27.22±3.37ml and24.88±3.04ml, respectively. A strong linear correlation was presented between the age and orbital volume (P<0.05). If stratified by age, the difference of orbital volume between the male and female was found not to be significant before14(P>0.05).
Conclusions There is no remarkable difference between the right and left orbital volume. Orbital volume is associated with age and gender. Orbital volume grows rapidly before20and still grows slowly after40.
引文
[1]Georgouli T, James T, Tanner S, et al. High-Resolution Microscopy Coil MR-Eye[J]. Eye,2008,22(8):994-996.
[2]Georgouli T, Chang B, Nelson M, et al. Use of High-Resolution Microscopy Coil MRI for Depicting Orbital Anatomy[J]. Orbit,2008,27(2):107-114.
[3]陈实,李颖,倪之挺.国人骨性眼眶的测量与观察[J].局解手术学杂志,1996,(54):1-2.
[4]李超,卢娜.成人骨性眼眶体积和断层测量[J].临床研究,2005,23(3):330-332.
[5]仁同明,宋艳东,宋艳梅,等.国人眼眶容积及骨性径线测量[J].解剖学研究,2002,24(3):208-231
[6]赵英,戴敏芳.MRI在眼眶病变中的应用[J].实用放射学杂志,2002,4(18):338-340.
[7]周全,黄力,刘斯润.眶部骨膜下区疾病的高分辨磁共振影像学表现[J].中华眼科杂志,2005,41(1):68-71.
[8]Ozgen A, Aydingoz U. Normative Measurements of Orbital Structures Using MRI[J]. J Comput Assist Tomogr,2000,24(3):493-496.
[9]Kolk A, Pautke C, Wiener E, et al. Isotropic proton-density-weighted high-resolution MRI for volume measurement of reconstructed orbital fractures-a comparison with multislice CT[J]. Magn Reson Imaging,2008,26(8): 1167-1174.
[10]Detorakis ET, Drakonaki E, Papadaki E, et al. Effective Orbital Volume and Eyeball Position:A MRI Study[J]. Orbit,2010,29(5):244-249.
[11]Tian S, Nishida Y, Isberg B, et al. MRI measurements of normal extraocular muscles and other orbital structures[J]. Graefes Arch Clin Exp Ophthalmol,2000, 238(5):393-404.
[12]Mark F, Conneel Y, Lotfi H, et al. Magnetic Resonance Imaging of the Orbit[J]. Seminars in Ophthalmology,2008,23(10):179-189.
[13]Krzizok TH, Schroeder BU. Measurement of recti eye muscle paths by magnetic resonsnce imaging in highly myopic and normal subjects[J]. Invest Ophthalmol Vis Sci,1999,40(11):2554-2560.
[14]惠延年.眼科学[M].第6版.北京:人民卫生出版社,2001:278-279.
[15]王振常.充分发挥现代影像技术在眼科临床工作中的作用[J].眼科,2007, 16(5):259-290.
[16]张明,鱼博浪,王泽忠,等.正常国人眼外肌的CT研究[J].中华放射学杂志,1999,33(11):772-774.
[17]Lee JS, Lim DW, Lee SH, et al.Normative measurement of Korean orbital Structure Srevealed by computerized tomography[J]. Aeta Ophthalmol Seand, 2001,79(2):197-200.
[18]李凤鸣.眼科全书[M].北京:人民卫生出版社,1996:2874.
[19]Kzrizok TH, Sehrodeer BU.Mesau rement of recti eye musele paths by magnetic resonsnce imaging in hignhly myopic and normal subjects[J].Invest Ophthalmol VisSci,1999,40(11):2554-2556.
[20]Dal Pozzo G, Boschi MC. Extraocular muscle enlargement in acromegaly[J]. J Comput Assist Tomogr,1982,6(4):706-707.
[21]Demer JL, Kerman BM. Comparison of standardized echography with magnetic resonance imaging to measure extraocular muscle size[J]. Am J Ophthalmol, 1993,118(3):351-361.
[22]Delint PJ, Mourits MP, Kerlen CH, et al. B-scan ultrasonography in Graxes orbitophy. Doc Ophthalmol,1993,85(1):1-4.
[23]胡聪.临床斜视诊断[M].北京:北京科学出版社,2001:215.
[24]Dermer J, Miller JM, Rosenbaum AL. Clinical correlations of models of orbitital statics[J]. In Proceedings of the Mechanics of Strabismus Symposium, San Francisco, Smith-Kettlewell Eye Research Institute,1992:141.
[25]Carteret M, Massin M, Cabanis EA. Stilling Duane syndrome and MRI:2 preliminary results[J]. J Fr Ophthalmol,1992,15(10):537-542.
[26]Polito E, Lecisotti A. MRI in Graves'orbitopathy:Recognition of enlarged muscle and prediction of steroid response[J]. Ophthalmological,1995,209(4): 182-186.
[27]Feldon SE, Weiner JM. Clinical significance of extra ocular muscle volumes in Graves'ophthalmopathy:a quantitative computed tomography study[J]. Arch Ophthalmol,1982,100(8):1266-1269.
[28]Laloux P, Mourain S, Buysschaert M. palpebral asymmetry and Graves' ophthalmopathy[J]. Acta Neurol Belg,1987,87(5):273-280.
[29]Scott IU, Siatkowski MR. Thyroid eye disease[J]. Semin Ophthalmol,1999, 14(2):52-61.
[30]Trokel SL, Jakobiec FA. Correlation of CT scanning and pathologic features of ophthalmic Graves'disease[J]. Ophthalmology,1981,88(6):553-564.
[31]Weber AL, Dallow RL, Sabates NR. Graves'disease of the orbit[J]. Neuroimaging Clin N Am,1996,6(1):61-72.
[32]李凤鸣.眼科全书[M].北京:人民卫生出版社,1996:2874.
[33]Morton AD, Elner VM, Lemke BN, et al. Lateral extensions of the Muller muscle[J]. Arch Ophthalmol,1996,114(12):1486-1488.
[34]田其昌,鲜军舫,王振常,等.MRI脂肪抑制和增强技术在诊断眼眶疾病中的应用[J].中华放射学杂志,1999,33(6):395.
[35]曾蒙苏,严福华,周康荣,等.磁共振动态增强和脂肪抑制技术在胰腺癌诊断中的价值[J].临床放射学杂志,2000,19(11):703.
[36]Ueno H, Ariji E, IzumiM, et al. MR imaging of the lacrimal gland.Age-related and gender-dependent changes in size and structure[J]. Acta Radiologica,1996, 37(5):714-719.
[37]乔宝笛,施明光.巩膜宽带环扎术后眼球三维形态的测量[J].临床研究,2007,25(8):612-615.
[38]GRASBONT, SCHRIEVERS, hoops JP, et al. Ultrasound Initial experience in various eye disease[J].Ophthalmology,2001,98(1):88-93.
[39]Berkowitz BA, Lukaszew RA, Mullins CM, et al. Impaired hyaloidal circulation function and uncoor dinated ocular grow thpatterns in experimental retinopathy of prematurity [J]. Invest Ophthalmol Vis Sci,1998,39 (2):391-396.
[40]Sawada T, Nakamura J, Nishida Y, et al Magnetic resonance imaging studies of the volume of the rabbit eye with intravenous mannitol[J]. Curr Eye Res,2002, 25(3):173-177.
[41]Chau A, Fung K, Pak K, et al. Is eye size related to or bit size in human subjects? [J]. Ophthalmic Physiol Opt,2004,24(1):35-40.
[42]Chau A, Fung K, Yap M. Evaluation of the accuracy of volume deter mination on the orbit and eyeball using MRI [J]. Radiography,2005,11 (1):35-39.
[43]Ramieri G, Spada MC, Bianchi SD, et al. Dimensions and volumes of the orbit and orbital fat in posttraumatic enophthalmos[J]. DentoMaxi FaciRadio,2000, 29(5):302-311.
[44]KeikoY, Minoru F. Orbital growth after unilateral enucleation in Infancy without an orbital implant[J]. Ophthalmol,2001,45(6):648-652.
[45]薛新生,应援宁,杨连海,等.爆裂性骨折所致眼球内陷的CT研究[J].天津医药,2003,31(1):20-22.
[46]Andreas K, Christoph P, Edzard W,et al. Isotropic proton-density-weighted high resolution MRI for volume measurement of reconstructed orbital fractures a comparison with multislice CT[J]. Magnetic Resonance Imaging,2008, (26): 1167-1174.
[47]Efstathios TD, Eleni D, Efrosini P, et al. Effective Orbital Volume and Eyeball Position:An MRI Study[J]. Effective Orbital Volume & Eyeball Position,2010, 29 (5):244-249.
[48]原林,骨学.见:柏树令.系统解剖学[M].北京:人民卫生出版社,2002:29.
[49]崔模,张朝佑.中国人骨性眼眶测量与观察(第一部分)[J].中华眼科杂志,1959,9:208.
[50]任同明,宋念东,宋艳梅,等.国人眼眶容积及骨性经线测量[J].解剖学研究,2002,24(3):208-231.
[51]Furuta M. Measurement of orbital volume by computed tomography-especially on the growth of orbit[J]. Jpn J Ophthalmol,2001,45(6):600-606.
[52]Hahn FJ, Chu WK. Ocular volume measured by CT scans[J]. J Neuroradio,1984, 26(6):419-420.
[53]吴景天.眼的解剖、生理和胚胎发育.见:严密,主编.眼科学[J].北京:人民卫生出版社,1997:25.
[1]刘淑贤,罗瑛.眼眶爆裂性骨折行羟基磷灰石修补术的护理[J].护理研究,2011,25(30):2794-2795.
[2]Ge WT, Zhou B, Han DM. Evaluation of imaging navigation system during endoscopic sinus surgery[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery,2006,26(8):565-569.
[3]陈文彬,潘祥林.诊断学[M].北京:人民卫生出版社,2004:23.
[4]王贵玉.多层螺旋CT后处理技术在眼眶骨折中的应用价值[J].中国实用医药,2011,(28):60-61.
[5]Singalavanija A, Amornrattanapan C, Nitiruangjarus K. Risk factors for retinal breaks in patients with symptom of floaters[J]. J Med Assoc Thai,2010,93(6): 708-713.
[6]Bencic G, Vatavuk Z, Marotti M. Comparison of A-scan and MRI for the measurement of axial length in silicone oil-filled eyes[J]. Br J Ophthalmol,2009, 93(4):502-505.
[7]徐海燕,金玉梅,李辉,等IOL-Master与A型超声测量前房深度和眼轴长度比较及其相关性[J].协和医学,2012,3(2):200-203.
[8]王富斌,王红,董丽梅.正常人视神经横断面积超声测量[J].临床眼科杂志,2002,10(2):142-143.
[9]徐亮(译).正常人及青光眼视神经的解剖结构.国外医学眼科学分册,1992,16:145.
[10]Dolan MS, Gala SS, Dodla S, et al. Safety and efficacy of commercially available ultrasound contrast agents for rest and stress echocardiography a multi-center experience[J]. J Am College of Car-diology,2009,18(9):63-64.
[11]杨瑞,代立梅,李剑颖.多层螺旋CT低剂量扫描在眼眶部外伤检查中的应用[J].中华放射学杂志,2010,44(7):731-734.
[12]康德强,赵晶,彭楠.辐射剂量个体化基础上降低64层CT冠状动脉成像扫描剂量的应用研究[J].中华放射学杂志,2012,46(3):234-238.
[13]李晓会,申富海,吴晓琴.低剂量CT扫描在儿童眼眶部疾病中的应用[J].实用放射学杂志,2010,26(6):916-917.
[14]Bursali A, Arac M, Oner AY, et al. Evalaution of the normal appendix at low-dose non-enhanced spiral CT[J]. Diagn Interv Radiol,2005,11(1):45-50.
[15]彭芸,李剑颖,马大庆.CT检查中低X射线剂量技术的应用和进展[J].中华放射学杂志,2008,42(10):1117-1120.
[16]刘长安,李小娟,高玲.辐射诱发白内障阈剂量判断:变化在即[J].中华放射医学与防护杂志,2011,31(3):249-251.
[17]顾小容,张兰芳,沈文荣.低Kv多层螺旋CT扫描技术的胸部应用[J].江苏医药,2007,33(12):1289-1290.
[18]穆学涛,王宏,钟心,等.MRI常规扫描结合扩散加权成像诊断眼眶淋巴瘤的价值[J].眼科新进展,2009,29(4):281-283.
[19]张小广,刘小琴,周琪,等.羟基磷灰石材料义眼台植入25例:传统与改良方法的比较[J].中国组织工程研究与临床康复,2010,14(47):8901-8903.
[20]李松年.现代全身CT诊断学[M].北京:中国医药科技出版社,1999:255.
[21]陈哲,郑晓华,谢宝君,等.不同年龄正常眼眶容积的CT测量[J].中华眼科杂志,2006,42(3):222-225.
[22]杨子权,祁吉,张文波,等.正常成人眼外肌的CT测量[J].中国医学影像学杂志,2000,8(3):181-183.
[23]王冬青,彭卫斌,殷瑞根,等.成人正常眼眶结构的CT测量[J].实用放射 学杂志,2002,18(7):582-584.
[24]Li S, Sun F, Jin ZY, et al. Whole-body diffusion-weighted imaging:technical improvement and preliminary results[J]. J Magn Reson Imaging,2007,26(4): 1139-1144.
[25]卢延,张雪哲.磁共振水成像[M].北京:科学出版社,2000:103-107.
[26]胡君.螺旋桨技术在头部磁共振扫描中应用优势及局限性分析[J].中国民康医学,2011,23(6):771-772.
[27]Black S, Iadecoh C. Vascular cognitive impairment:small vessels, big toll: introduction[J]. Stroke,2009,40(3 Suppl):S38-9.
[28]曾蒙苏,严福华,周康荣,等.磁共振动态增强和脂肪抑制技术在胰腺癌诊断中的价值.临床放射学杂志,2000,19(11):703-706.
[29]于文玲,王振常,李静,等.正常人泪腺MRI研究[J].临床放射学杂志,2010,29(4):448-451.
[30]张光明,熊茵,胡燕华,等.中国汉族人正常眼眶结构的MRI测定[J].华中科技大学学报(医学版).2004,33(3):363-365,375.
[31]任亚琳,王利华,于骀飞.MIR测量正常人眼眶直肌坐标值及眼球动态直肌横截面积的研究[J].中国斜视与小儿眼科杂志,2005,13(3):97-101
[1]Dwivedi Y, Rastogi R, Sharma SK, et al. Picroliv affords protection against thioacetamide-induced hepatic damage in rats[J]. Planta Med,1991,57(1):25-28.
[2]Hsu YC, Chiu YT, Cheng CC, et al. Antifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver fibrosis. J Gastroenterol Hepatol,2007,22(1): 99-111.
[3]Chang JW, K im CS, K im SB, et al. Proinflammatory cytokine induced NF-kappa B activation in humanm esangial cells ism ediated through intracellular calcium but not ROS:effects of silymarin[J]. Nephron Exp Nephrol, 2006,103(4):156-165.
[4]Kang JS, Jeon Y J, Park SK, et al. Protection again st lipopolysaccharide-induced seps is and inhibit ion of interleukin-lbeta and prostagland in E2 synthes is by silym arin[J]. Biochem Pharmacol,2004,67(1):175-181.
[5]Skorupski KA, Hammond GM, Irish AM, et al. Prospective randomized clinical trial assessing the efficacy of Denamarin for prevention of CCNU-induced hepatopathy in tumor-bearing dogs[J]. J Vet Intern Med,2011,25(4):838-845.
[6]Raskovic A, Stilinovic N, Kolarovic J, et al. The Protective Effects of Silymarin against Doxorubicin-Induced Cardiotoxicity and Hepatotoxicity in Rats[J]. Molecules,2011,16(10):8601-8613.
[7]Parveen R, Baboota S, Ali J, et al. Effects of silymarin nanoemulsion against carbon tetrachloride-induced hepatic damage[J]. Arch Pharm Res,2011,34(5): 767-774.
[8]Au AY, Hasenwinkel JM, Frondoza CG. Hepatoprotective effects of S-adenosylmethionine and silybin on canine hepatocytes in vitro[J]. J Anim Physiol Anim Nutr (Berl),2012,97(2):331-341.
[9]Trappoliere M, Caligiuri A, Schmid M, et al. Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells[J]. J Hepatol,2009,50(6):1102-1111.
[10]Falasca K, Ucciferri C, Mancino P, et al. Treatment With Silybin-Vitamin E-Phospholipid Complex in Patients With Hepatitis C Infection[J]. J Med Virol, 2008,80(11):1900-1906.
[11]Biermer M, Berg T. Rapid Suppression of Hepatitis C Viremia Induced by Intravenous Silibinin Plus Ribavirin[J]. Gastroenterology,2009,137(1):390-391.
[12]Eurich D, Bahra M, Berg T, et al. Treatment of Hepatitis C-Virus-Reinfection After Liver Transplant with Silibinin in Nonresponders to Pegylated Interferon-based Therapy [J]. Exp Clin Transplant,2011,9(1):1-6.
[13]Rutter K, Scherzer TM, Beinhardt S, et al. Intravenous silibinin as'rescue treatment'for on-treatment non-responders to pegylated interferon/ribavirin combination therapy[J]. Antivir Ther,2011,16(8):1327-1333.
[14]Wagoner J, Morishima C, Graf TN, et al. Differential In Vitro Effects of Intravenous versus Oral Formulations of Silibinin on the HCV Life Cycle and Inflammation[J]. PLoS One,2011,6(1):e16464.
[15]Hawke RL, Schrieber SJ, Soule TA, et al.Silymarin Ascending Multiple Oral Dosing Phase I Study in Noncirrhotic Patients With Chronic Hepatitis C[J]. J Clin Pharmacol,2010,50(4):434-449.
[16]Ahmed-Belkacem A, Ahnou N, Barbotte L, et al. Silibinin and Related Compounds Are Direct Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase[J]. Gastroenterology,2010,138(3):1112-1122.
[17]Polyak SJ, Morishima C, Lohmann V, et al. Identification of hepatoprotective flavonolignans from silymarin[J]. Proc Natl Acad Sci USA,2010,107(13): 5995-5999.
[18]Kohno H, Tanaka T, Kawabata K, et al. Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane induced colon carcinogenesis in male F344 rats[J]. Int J Cancer,2002,101(5):461-468.
[19]Singh RP, Dhanalakshmi S, Tyagi AK, et al. Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels[J]. Cancer Res,2002, 62(11):3063-3069.
[20]Zi X, Feyes DK, Agarwal R. Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468:induction of G1 arrest through an increase in Cipl/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins[J]. Clin Cancer Res,1998,4(4): 1055-1064.
[21]Varghese L, Agarwal C, Tyagi A, et al. Silibinin efficacy against human hepatocellular carcinoma[J]. Clin Cancer Res,2005,11(23):8441-8448.
[22]Ramakrishnan G, Raghavendran HR, Vinodhkumar R, et al. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats[J]. Chem Biol Interact,2006,161(2):104-114.
[23]Lah JJ, Cui W, Hu KQ. Effects and mechanisms of silibinin on human hepatoma cell lines[J]. World J Gastroenterol,2007,13(40):5299-5305.
[24]Chen CH, Huang TS, Wong CH, et al.Synergistic anti-cancer effect of baicalein and silymarin on human hepatoma HepG2 Cells[J]. Food Chem Toxicol,2009, 47(3):638-644.
[25]Brandon-Warner E, Sugg JA, Schrum LW, et al. Silibinin inhibits ethanol metabolism and ethanol-dependent cell proliferation in an in vitro model of hepatocellular carcinoma[J]. Cancer Lett,2010,291(1):120-129.
[26]Angeli JP, Barcelos GR, Serpeloni JM, et al. Evaluation of the genotoxic and anti-genotoxic activities of Silybin in human hepatoma cells (HepG2)[J]. Mutagenesis,2010,25(3):223-229.
[27]Wu YF, Fu SL, Kao CH, et al., Chemopreventive Effect of Silymarin on Liver Pathology in HBV X Protein Transgenic Mice[J]. Cancer Res,2008,68(6): 2033-2042.
[28]Schumann J, Prockl J, Kiemer AK, et al. Silibinin protects mice from T cell-dependent liver injury[J]. J Hepatol,2003,39(3):333-340.
[29]Kim CS, Choi SJ, Park CY, et al. Effects of Silybinin on the Pharmacokinetics of Tamoxifen and Its Active Metabolite,4-Hydroxytamoxifen in Rats[J]. Anticancer Res,2010,30(1):79-85.