特定寡核苷酸对大鼠实验性牙移动骨改建影响作用的研究
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摘要
目的:
通过局部注射特定寡核苷酸(oligodeoxynucleotides, ODN),观察大鼠实验性牙移动的距离及牙周组织形态的变化,检测局部牙周组织中RANKL和Ⅰ型胶原的表达,探讨特定ODN对大鼠实验性牙移动骨改建的影响作用。
方法:
选用7周龄SPF级健康雄性Wistar大鼠40只,体重221±18g,随机分为实验组与对照组,每组20只。建立实验性大鼠牙移动模型,以上颌切牙为支抗,40g力拉上颌第一磨牙向近中移动。加力当天于实验组大鼠两侧上颌第一磨牙颊侧牙龈黏膜下各注射特定ODN MT01(20μg/ml)50μl,对照组大鼠相同部位注射等量的PBS溶液。每3d给药一次。取加力3d、7d、14d、21d、28d五个时间点每组各处死4只大鼠。两组大鼠均于牙移动装置安置前和处死前取印模,制作超硬石膏模型后测定牙移动距离;并于心脏灌注处死后取上颌第一磨牙及其周围牙周组织制作石蜡切片,经HE染色观察牙周组织形态变化并进行破骨细胞计数,经免疫组织化学染色图像分析观察RANKL和Ⅰ型胶原表达水平的变化。
结果:
①实验组除加力3d外,其他各观察时间点大鼠第一磨牙牙移动距离均小于对照组,差异有统计学意义(P<0.05);
②HE染色观察显示,实验组大鼠第一磨牙压力侧牙槽骨吸收程度轻于对照组,且破骨细胞数也少于对照组,其中3d、7d时差异最显著(P<0.01);
③免疫组织化学图像分析显示,实验组与对照组大鼠第一磨牙牙周组织Ⅰ型胶原的表达水平呈逐渐增加至14d达到峰值后降低的趋势,且实验组Ⅰ型胶原阳性表达的平均光密度值全程大于对照组,7d、14d、21d时有显著差异(p<0.05);实验组和对照组RANKL的表达水平呈7d时达峰值,而后逐渐降低的趋势,且各观察时点实验组RANKL阳性表达的平均光密度值均小于对照组,7d、14d两组间差异显著(p<0.01),21d、28d时差异无统计学意义。
结论:
在大鼠实验性牙移动过程中,特定ODN减少了压力侧牙槽骨表面破骨细胞的数量,抑制了实验性牙齿移动;特定ODN还增强了牙周组织内Ⅰ型胶原的表达并减弱了RANKL的表达,进一步证实特定ODN对大鼠实验性牙移动骨改建具有影响作用。
Objective:
The purpose of the present experiment is to study the effect of the specific sequence oligonucleotide (oligodeoxynucleotides, ODN) on the distances of tooth movement ;to study the changes of periodontium structure, and the expressions of RANKL and typeⅠcollagen which are contained in the periodontal tissue of the rats;then to investigate the effect of this specific ODN on the control of tooth movement and alveolar bone remodeling.
Method:
40 male Wister rats which were 7 weeks old (weight 221±18g) were randomly divided into experimental group and control group, n = 20. then according to the observation point, each group was divided into 3d, 7d , 14d, 21d, and 28d’s observation group,n=4. Under the anchorage of rats’maxillary front teeth, established model of experimental tooth movement in rats in order to pull the maxillary first molar move mesial by the force of 40g.After that, the buccal gingival mucosa of the maxillary first molar of the experimental group was injected with 50μl ODN (20μg/ml), and the control group was injected with the same amount of PBS, administered once every 3d. The rats of each observation group of the experimental group and control group were killed on its observation point. The plaster models of rats’upper mandible were made to measure the distance of tooth movement , afer the tooth moving models were erected and before tha rats were killed.Then the maxillary first molar and its periodontium were got from the dead rats.By the way of HE stain and immunohistochemistry stain to observe the changes of periodontium structure, and the expressions of RANKL and typeⅠcollagen which were contained in the periodontal tissue.
Results:
①Besides the 3rd day , the moving distances of the first molars of the experimental groups were less than the control group, and the difference was statistically significant (P <0.05).
②HE staining showed that the absorption of pressure side of the first molar alveolar bone in the the experimental group was less than the control group.Furthermore the number of osteoclasts was also less than the control group,especially the 7 th day (P <0.01).
③The image of immunohistochemistry staining revealed that expression of typeⅠcollagen , which was contained in the periodontal tissue of rats ,gradually increased to peak in the 14 th day, then decreased.The collagen typeⅠin the experimental group was greater than the control group, especially the day of 7 th,14 th and 21th(p <0.05).But the expression of RANKL in periodontium of both the experimental group and control group had its peak in the 7 th day,and then gradually decreased. Moreover the expression of RANKL of the experimental group were less than the control group, especially the day of 7 th,14 th and 21th (p <0.01),But in the day of 21 th and 28 th the the difference between the two groups had not statistically significant.
Conclusion:
In rats model of experimental tooth movement, the specific ODN can reduce the number of osteoclasts on the pressure side of the alveolar bone surface and inhibit experimental tooth movement. After that this specific ODN can also enhance the expression of typeⅠcollagen and reduce the expression of RANKL, which were contained by periodontal tissue. All of these show that the specific ODN can affect on the control of tooth movement and alveolar bone remodeling.
通过局部注射特定寡核苷酸(oligodeoxynucleotides, ODN),观察大鼠实验性牙移动的距离及牙周组织形态的变化,检测局部牙周组织中RANKL和Ⅰ型胶原的表达,探讨特定ODN对大鼠实验性牙移动骨改建的影响作用。
方法:
选用7周龄SPF级健康雄性Wistar大鼠40只,体重221±18g,随机分为实验组与对照组,每组20只。建立实验性大鼠牙移动模型,以上颌切牙为支抗,40g力拉上颌第一磨牙向近中移动。加力当天于实验组大鼠两侧上颌第一磨牙颊侧牙龈黏膜下各注射特定ODN MT01(20μg/ml)50μl,对照组大鼠相同部位注射等量的PBS溶液。每3d给药一次。取加力3d、7d、14d、21d、28d五个时间点每组各处死4只大鼠。两组大鼠均于牙移动装置安置前和处死前取印模,制作超硬石膏模型后测定牙移动距离;并于心脏灌注处死后取上颌第一磨牙及其周围牙周组织制作石蜡切片,经HE染色观察牙周组织形态变化并进行破骨细胞计数,经免疫组织化学染色图像分析观察RANKL和Ⅰ型胶原表达水平的变化。
结果:
①实验组除加力3d外,其他各观察时间点大鼠第一磨牙牙移动距离均小于对照组,差异有统计学意义(P<0.05);
②HE染色观察显示,实验组大鼠第一磨牙压力侧牙槽骨吸收程度轻于对照组,且破骨细胞数也少于对照组,其中3d、7d时差异最显著(P<0.01);
③免疫组织化学图像分析显示,实验组与对照组大鼠第一磨牙牙周组织Ⅰ型胶原的表达水平呈逐渐增加至14d达到峰值后降低的趋势,且实验组Ⅰ型胶原阳性表达的平均光密度值全程大于对照组,7d、14d、21d时有显著差异(p<0.05);实验组和对照组RANKL的表达水平呈7d时达峰值,而后逐渐降低的趋势,且各观察时点实验组RANKL阳性表达的平均光密度值均小于对照组,7d、14d两组间差异显著(p<0.01),21d、28d时差异无统计学意义。
结论:
在大鼠实验性牙移动过程中,特定ODN减少了压力侧牙槽骨表面破骨细胞的数量,抑制了实验性牙齿移动;特定ODN还增强了牙周组织内Ⅰ型胶原的表达并减弱了RANKL的表达,进一步证实特定ODN对大鼠实验性牙移动骨改建具有影响作用。
Objective:
The purpose of the present experiment is to study the effect of the specific sequence oligonucleotide (oligodeoxynucleotides, ODN) on the distances of tooth movement ;to study the changes of periodontium structure, and the expressions of RANKL and typeⅠcollagen which are contained in the periodontal tissue of the rats;then to investigate the effect of this specific ODN on the control of tooth movement and alveolar bone remodeling.
Method:
40 male Wister rats which were 7 weeks old (weight 221±18g) were randomly divided into experimental group and control group, n = 20. then according to the observation point, each group was divided into 3d, 7d , 14d, 21d, and 28d’s observation group,n=4. Under the anchorage of rats’maxillary front teeth, established model of experimental tooth movement in rats in order to pull the maxillary first molar move mesial by the force of 40g.After that, the buccal gingival mucosa of the maxillary first molar of the experimental group was injected with 50μl ODN (20μg/ml), and the control group was injected with the same amount of PBS, administered once every 3d. The rats of each observation group of the experimental group and control group were killed on its observation point. The plaster models of rats’upper mandible were made to measure the distance of tooth movement , afer the tooth moving models were erected and before tha rats were killed.Then the maxillary first molar and its periodontium were got from the dead rats.By the way of HE stain and immunohistochemistry stain to observe the changes of periodontium structure, and the expressions of RANKL and typeⅠcollagen which were contained in the periodontal tissue.
Results:
①Besides the 3rd day , the moving distances of the first molars of the experimental groups were less than the control group, and the difference was statistically significant (P <0.05).
②HE staining showed that the absorption of pressure side of the first molar alveolar bone in the the experimental group was less than the control group.Furthermore the number of osteoclasts was also less than the control group,especially the 7 th day (P <0.01).
③The image of immunohistochemistry staining revealed that expression of typeⅠcollagen , which was contained in the periodontal tissue of rats ,gradually increased to peak in the 14 th day, then decreased.The collagen typeⅠin the experimental group was greater than the control group, especially the day of 7 th,14 th and 21th(p <0.05).But the expression of RANKL in periodontium of both the experimental group and control group had its peak in the 7 th day,and then gradually decreased. Moreover the expression of RANKL of the experimental group were less than the control group, especially the day of 7 th,14 th and 21th (p <0.01),But in the day of 21 th and 28 th the the difference between the two groups had not statistically significant.
Conclusion:
In rats model of experimental tooth movement, the specific ODN can reduce the number of osteoclasts on the pressure side of the alveolar bone surface and inhibit experimental tooth movement. After that this specific ODN can also enhance the expression of typeⅠcollagen and reduce the expression of RANKL, which were contained by periodontal tissue. All of these show that the specific ODN can affect on the control of tooth movement and alveolar bone remodeling.
引文
[1]郊静,唐卫忠,汪大林.正畸牙移动的影响因素[J].现代口腔医学杂志2006,20(40):429-431.
[2]孙新华,朱宪春,徐成伟等.弱激光照射对兔牙移动速度及骨改建影响的实验研究[J].华西口腔医学杂志,2001,19(5):290-293.
[3]康祖铭,李春梅,石君等.旋转脉动磁场对兔正畸牙槽骨改建的影响[J].吉首大学学报(自然科学版).2010,31(2):108-110.
[4]廖建宏.超声波对正畸牙移动过程中牙龈血流量影响的临床研究[J].临床口腔医学杂志,2006,22(1):41-42.
[5]刘畅,孙新华,陈远萍等.局部应用二磷酸盐对鼠正畸牙移动影响的研究[J].中华口腔医学杂志,2002,37(4):290-293.
[6] Guanghong Han,Yuanping Chen,Jianhua Hou,et al. Effects of simvastatin on relapse and remodeling of periodontal tissues after tooth movement in rats [J]. American Journal of Orthodontics and Dentofacial Orthopedics,2010, 138, (5):550e1-550e7.
[7]沈刚,陈荣敬,刘侃.药物加速矫治牙移动的机理探讨[J].口腔医学,1993,13(1):47-48.
[8] Jeremy C. Karrasa, James R. Millerb, James S. Hodgesc.et al. Effect of alendronate on orthodontic tooth movement in rats[J]. American Journal of Orthodontics and Dentofacial Orthopedics,2009,136(6):843-847.
[9] Theodosia Bartzela, Jens C. Türp,Edith Motschall,et al. Medication effects on the rate of orthodontic tooth movement: A systematic literature review[J]. Am J Orthod Dentofacial Orthop, 2009,135(1):16-26.
[10]丁寅,陈华,徐如生.消炎痛对正畸牙齿移动影响的研究[J].口腔正畸学杂志,1994,1(2):80-81.
[11]冯江,万虎,吴耀禄.非甾体抗炎药致肝肾损害10例临床分析[J].陕西医学杂志,2000,29(2):118-119.
[12] J.J. Zahrowski.Bisphosphonate treatment: an orthodontic concern calling for a proactive approach [J], Am J Orthod Dentofacial ,2007: 311–320.
[13] Tokunaga T,Yano O,Kuramoto E,et a1.Synthetic oligonucleotides with particular base sequences from the eDNA encoding proteins of Mycobacerium bovis BCG induce intefereon and activate natural killer cells [J].Microbiol Immunol,1992,36(1):55-66.
[14] Han-A Kim,Hyun-Mi Ko,Hye-Won Ju,et al. CpG-ODN-based immunotherapy is effective in controlling the growth of metastasized tumor cells [J]. Cancer Letters, 2009,274 :160–164.
[15] Chun-sheng Liu ,Yun Sun,Yong-hua Hu,et al. Identification and analysis of the immune effects of CpG motifs that protect Japanese flounder (Paralichthys olivaceus) against bacterial infection [J]. Fish & Shellfish Immunology ,2010:1-7.
[16]李四堂,何知. CpG ODN与哮喘免疫治疗进展[J].江西医药,2009,44(10):1020-1022.
[17] HemmiH,TakeuchiO,KawaiT,et al.A Toll-like receptor recognizes bacterial DNA [J].Nature, 2000, 408(6813): 740-745.
[18]司兴奎,陈建红,张济培等. CpG寡脱氧核苷酸的免疫刺激特性及应用研究进展[J].动物医学进展,200,29(7):71-75.
[19] Krieg AM, Wu T, Weeratna R, et al. Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs[J. Proc Natl Acad Sci USA, 1998, 95(21): 12631-12636.
[20] Stunz LL, Lenert P, Peckham D, et al. Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells[J]. Eur J Immunol, 2002, 32(5): 1212-1222.
[21]王瑾,张王刚.CpG ODN序列结构特征对免疫活性影响的研究进展[J].细胞与分子免疫学杂志,2008,24(12):1219-1221.
[22]金伯泉.固有免疫中模式识别受体及其信号转导一当代免疫学中最伟大的发现之一[J].细胞与分子免疫学杂志,2006,22(1):1-3.
[23]钱旭波,蔡晓红. Toll样受体9及其配体研究进展[J].医学综述,2010,16(19):2886-2887.
[24] Akira S.TLR signaling.Curr Top Microbiol Immunol,2006,311:1.
[25]冯涛. TLR9的结构、功能及信号传导研究进展[J].国外医学免疫学分册,2005,28(2 ):72-76.
[26] Andor Pivarcsi.Toll-Like Receptor 9-Independent Suppression of Skin Inflammation by Oligonucleotides [J].Journal of Investigative Dermatology,2007,127: 746–748.
[27] Arash Ronaghy,Berent J.Prakken,Kenji Takabayashi,et al.Immunostimulatory DNA Sequences Influence the Course of Adjuvant Arthritis1 [J].The Journal ofImmunology,2002,168:51–56.
[28] Dennis Klinman,Hidekazu Shirota,Debra Tross,et al.Synthetic oligonucleotides as modulators of inflammation [J].J Leukoc Biol,2008,84(4):958–964.
[29] Weronika Rudnicka,Tomasz Burakowski,Ewa Warnawin.Functional TLR9 modulates bone marrow B cells from rheumatoid arthritis patients [J].Eur. J. Immunol,2009,39:211–1220.
[30]王凌,李大金.Toll样受体在成骨细胞和破骨细胞中的表达及作用[J].国外医学内分泌学分册,2005,25(5):330-332.
[31] Nemoto E, Honda T, Kanaya S,et al. Expression of functional Toll-like receptors and nucleotide-binding oligomerization domain proteins in murine cementoblasts and their upregulation during cell differentiation. J Periodont Res 2008; 43: 585–593.
[32]胡楠,何文喜,王玮等. TLR9在成牙本质细胞中的表达[J].口腔医学研究,2010,26(4):464-466.
[33] Wei Zou,Harry Schwartz,Stefan Endres,et al.CpG oligonucleotides: Novel regulators of osteoclast differentiation [J].FASEB J,2002,16:274–282.
[34]赵为公,韩学哲,刘淼等.富含CpG的脱氧核苷酸片段对破骨细胞形成的调节作用[J].第四军医大学学报,2004,25(15):1386-1388.
[35] Masako Yoshimatsu,Hideki Kitaura,et al.IL-12 inhibits TNF-αinduced osteoclasto- genesis via a T cell-independent mechanism in vivo [J].Bone,2009,45(5): 1010- 1016.
[36] Alla Amcheslavsky,Zvi Bar-Shavit.Interleukin (IL)-12 Mediates the Anti- Osteoclastogenic Activity of CpG- Oligodeoxynucleotides [J].Journal of Cellular Physiology,2006,207:244–250.
[37] Alla Amcheslavsky,Zvi Bar-Shavit.Toll-Like Receptor 9 Ligand Blocks Osteoclast Differentiation Through Induction of Phosphatase [J].J Bone Miner Res,2007,22: 1301–1310.
[38] Jae-Ho Chang a, Eun-Ju Chang c, Hong-Hee Kim c,et al.Enhanced inhibitory effects of a novel CpG motif on osteoclast differentiation via TREM-2 down–regulation [J].Biochemical and Biophysical Research Communications ,2009, 389:28–33.
[39] Wei Zou,Alla Amcheslavsky,and Zvi Bar-Shavit.CpG oligodeoxynucleotides modulate the osteoclastogenic activity of osteoblasts via toll-like receptor 9 [J].The Journal of Biological Chemistry,2003,278(19):16732-16740.
[40] Alla Amcheslavsky,Hiroaki Hemmi,Shizuo Akira,et al .Differential Contributionof Osteoclast- and Osteoblast-Lineage Cells to CpG-Oligodeoxynucleotide (CpG-ODN) Modulation of Osteoclastogenesis [J].J Bone Miner Res,2005,20:1692– 1699.
[41]申玉芹,孙新华,于丽等.不同CpG ODN对大鼠骨髓间充质干细胞增殖作用的研究[J].口腔医学研究,2009,25(6):723-725.
[42]申玉芹,孙新华,于丽等.小寡核苷酸对大鼠骨髓间充质干细胞向成骨细胞分化的影响[J].吉林大学学报(医学版),2010,36(2):336-339.
[43]申玉芹.寡核苷酸(ODN)促骨髓间充质干细胞向成骨细胞分化作用及机制研究[D].吉林:吉林大学口腔医学院,2010.
[44] Guang Yang,Min Wan,Yongsheng Zhang,te al. Inhibition of a C-rich oligodeoxynucleotide on activation of immune cells in vitro and enhancement of antibody response in mice[J]. mmunology, 2010,131, 501–512.
[45]杨光.富含胞嗜陡的脱氧寡核普酸对免疫反应的负调节作用[D].吉林,吉林大学白求恩医学院,2009
[46] King GJ,Keeling SD,McCoy EA,et al.Measuring dental drift and orthodontic tooth movement in response to various initial forces in adult rat [J].Am J Orthod Dentofacial Orthop,1991,99(5):456-465.
[47] YAMASAKI K, MIURA F,SUDA T. Prostaglandin as a mediator of bone resorption induced by experimental tooth movement in rats[J]. J Dent Res, 1980, 59:1635-1642.
[48]丁寅,陈华,徐如生.中药丹参加速正畸牙齿移动的研究[J].口腔医学,1995,15(3):120-121.
[49]华咏梅,王宏伟,牟福元.可溶性白细胞介素-1和肿瘤坏死因子受体对大鼠正畸牙移动影响的研究.华西口腔医学杂志,2008, 26(2):189-193.
[50] Kim TW,Yoshide Y,Yokoya K,et al.An ultrastructural study of the effects of bisphosphonate administration on osteoclastic bone resorption during relapse of experimentally moved rat molars.Am J Orthod Dentofac Orthop,1999,115:645-653.
[51]韩光红,陈远萍,侯建华等.辛伐他汀抑制正畸牙齿移动后复发距离的实验研究[J].现代口腔医学杂志,2006,20(6):621-623.
[52] Tokunaga T,Yano O,Kuramoto E,et a1.Synthetic oligonucleotides with particular base sequences from the eDNA encoding proteins of Mycobacerium bovis BCG induce intefereon and activate natural killer cells [J].Microbiol Immunol,1992,36(1): 55-66.
[53]任继玲.动物特异性CpG ODN的设计、筛选及对疫苗的增效作用[D].吉林:吉林大学白求恩医学院,2010.
[54] Krieg AM,Hartmann G,Yi AK.Mechanisms of action of CpG DNA[J].Curr Top Microbio Immunol,2000,247:l-21.
[55] Krieg.A.M,Yi A.K,Sehorr J.The role of CpG deoxynueleotides in DNA vaceine [J]. Trends. Mierobiol,1998,6:23-27.
[56] Kamstrup S,Verthelyi D,Klinman DM. Response of porcine peripheral blood mononuclear cells to CPG-containing oligodeognlileotides [J].Vet Microbiol,2001:78(4): 353-62.
[57] Hrtmann G,Krieg AM.Mechanism and function of a newly identified CPG DNA motif in human Primary B cells [J].J Immunol,2000,164:944-952.
[58] Hartmann G, Weeratna RD, Ballas ZK, Payette P, Blackwell S, Suparto I, et al. Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo [J] .J Immunol,2000 , 164(3):1617-1624.
[59] Mutwiri G, Pontarollo R, Babiuk S, et al. Biological activity of immunostimulatory CpG DNA motifs in domestic animals[J]. Vet Immunol Immunopathol, 2003,91(2):89-103.
[60] Nichani AK, Kaushik RS, Mena A, Popowych Y, Dent D, Townsend HG, et al. CpG oligodeoxynucleotide induction of antiviral effector molecules in sheep [J]. Cell Immunol,2004 ,227(1):24-37.
[61] Gunther H,Risini D.Delineation of a CpG phophorothioate Oligodeoxynueleo- tide for Activating Primate Immune Response In vitor and In vivo [J].The Joumal of Immunology. 2000,164,1617-1624.
[62]许洪林,王四清,王世峰.利用小鼠模型评价含5-GTC GTT-3特征序列的人CpG寡脱氧核苷酸免疫刺激活性[J].病毒学报.2001,17(l): 43-47.
[63]季颖,江志强.口腔黏膜给药系统研究进展[J].中国生化药物杂志,2003,24,(3):150-152.
[64]李丁,王健,侯惠民.口腔黏膜给药系统研究进展[J].中国医药工业杂志,2009,40,(4):303-307.
[65] Suna Wang,Qunying Han,Ni Zhang,et al. HBcAg18–27 epitope fused to HIV-Tat49–57 adjuvanted with CpG ODN induces immunotherapeutic effects in transgenic mice[J]. Immunology Letters,2010,127:143–149.
[66] Hui Zhang, Quan Gong , Jun-hua Li,et al. CpG ODN pretreatment attenuates concanavalin A-induced hepatitis in mice[J]. International Immunopharmaco- logy,2010, 10:79–85.
[67] Maria Pihlgren, Chantal Tougne, Nadine Schallert,et al. CpG-motifs enhance initial and sustained primary tetanus-specific antibody secreting cell responses in spleen and bone marrow, but are more effective in adult than in neonatal mice [J]. Vaccine, 2003,21:2492–2499.
[68] Arthur M Krieg. A possible cause of joint destruction in septic arthritis[J]. Arthritis Research,1999, 1(1):3-4.
[69]郭莹莹.CpG ODN在OVA诱导的哮喘小鼠模型中的治疗作用[D].吉林:吉林大学白求恩医学院,2010.
[70] Daniel E. Speiser, Danielle Liénard,Nathalie Rufer,et al. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleo- tide 7909 [J]. J Clin Invest. 2005, 115(3): 739–746.
[71] Molenkamp BG,van Leeuwen PA.Meijer S,et a1.Intradermal CpG-B activates both plasmaeytoid and myeloid dendritic cells in the sentinel lymph node of melanoma patients[J].Clin Cancer Res,2007,13(10):2961-2969.
[72] Krieg AM. CpG motifs in bacterial DNA and their immune effects [J]. Annu Rev Immunol, 2002,20:709-60.
[73] wilson Hg.Dar A,Napper SK.et a1.Immune mechanisms and therapeutic potential of CpG oligodeoxynucleotides[J].Int Rev Immunol,2006,25(3-4):183-213.
[74]宋光,张卓然.CpG寡核苷酸的安全性实验研究[J].中国微生态学杂志,2004,16 (6):321- 326.
[75] Hartmann G, Weeratna RD, Ballas ZK, Payette P, Blackwell S, Suparto I, et al. Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo. [J] J Immunol. 2000 Feb 1;164(3):1617-1624.
[76]何威,周佩军,沈周俊.新型的免疫佐剂:CpG寡聚脱氧核苷酸[J].中国临床医学,2008,15(5):673-676.
[77] Bourauel C, Freudenreich D, Vollmer D, et al. Simulation of orthodontic tooth movements. A comparison of numerical models[J]. J Orofac Orthop,1999, 60(2): 136-151.
[78] Zeuner RA, Ishii KJ, Lizak MJ, Gursel I, Yamada H, Klinman DM, et al.Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides [J]. Arthritis Rheum 2002;46:2219-24.
[79] Li Dong, Shu-ichi Ito, Ken J. Ishii,et al. Suppressive Oligonucleotides Protect Against Collagen-Induced Arthritis in Mice [J]. ARTHRITIS & RHEUMATISM , 2004, 50(5): 1686–1689.
[80] Brudvik P , Rygh P. The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament [J] . Eur J Orthod ,1993 ,15 :2249- 2263.
[81] Thomas MJ, Robert L. Orthodontics-Current principle and techniques[J].Orthod Waves. 1999,58:416-427.
[82] Nonglak P. Sombunthama, Siriwan Songwattanab, Phumvuth Atthakornc, Sumon Jungudomjaroend and Busaba Panyarachune. Early tooth movement with a clear plastic appliance in rats [J].American Journal of Orthodontics and Dentofacial Orthopedics,2009, 136( 1): 75-82.
[83]郭力嘉.正畸牙齿移动过程中破骨细胞表达的动物实验研究[D].硕士.辽宁:大连医科大学,2009.
[84] Zhang Y H, Heulsmann A, TondraviM M, et al. Tumor necrosis factor-alpha ( TNF) stimulates RANKL-induced osteoclastogenesis via coup ling of TNF type I recep tor and RANK signaling pathways [ J ]. J Biol Chem, 2001, 276 (1) : 563-568.
[85] Wada T, Nakashima T, Hiroshi N, et al. RANKL-RANK signaling in osteoclastogenesis and bone disease [ J ]. TrendsMolMed,2006, 12 (1) : 17-25.
[86]刘长庚,凌天牖,黄生高.OPG/RANKL /RANK系统及其临床应用[J].国际病理科学与临床杂志,2007,27(6):534-538.
[87]郝鹏杰,李建昌,王霄立等.不同浓度1,25-二羟基维生素D3对大鼠正畸牙移动速度的影响[J].广东牙病防治,2008,16(8):348-350.
[88] Lee WC.Experimental study of the effect of prostaglandin administration on the tooth movement with particular emphasis on the relationship to the method of PGE1 administration [J].Am J Orthod Dentofacial Orthop,1990,98:231-241.
[89]裘松波,杨健,谭颖徽.核因子-κB受体活化因子配体在大鼠正畸牙压力侧牙周组织中的表达[J].牙体牙髓牙周病学杂志,2005,15(2):76-79.
[90] Yamauchi, E.P. Katz and G.L. Mechanic, Intermolecular crosslinking and stereospecific molecular packing in type I collagen fibrils of the periodontal ligament [J].Biochemistry,1986, 25: 4907–4913.
[91] Sodek and J.M. Ferrier, Collagen remodelling in rat periodontal tissues: compensation for precursor reutilization confirms rapid turnover of collagen [J].Coll. Relat, 1988,1 : 11–21.
[92] Sutherland MSK, Rao L G, Muzaffar SA , et al. Age2 dependent expression of osteoblastic phenotypic markers in normal human osteoblasts cultured Long term in the presence of dexamethasone [J] . Osteo porosis Int , 1995 , 5 :335-343.
[93]王海彬,何伟,袁浩.成骨细胞和Ⅰ型胶原.中国中医骨伤科杂志,2003,11(3):56-58.
[94] Scheven BA, Hamilton NJ, Farquharson C, et al. Immunohistochemical localization of native and denatured collagen typesⅠa ndⅡin fetal and adult rat long bones [J].Bone, 1988,9(6):407-14.
[95] NAKAGAWAM, KUKITAT, NAKASIMA A, et al. Expression of the type I collagen gene in rat periodontal ligament during tooth movement as revealed by in situ hybridization [J]. ArchOral Biol, 1994,39(4):289-294.
[96] BUMANN A, CARVALHO R S, SCHWARZER C L, et al. Collagen synthesis from human PDL cells following orthodontic tooth movement [J].Eur J Orthod, 1997,19(1):29-37.
[97] FUKUI T, YAMANEA, KOMATSUK, et al. Restoration of mechanical strength and morphological features of the periodontal ligament following orthodontic retention in the rat mandibular first molar [J]. Eur J Orthod,2003,25(2):167-174.
[98]刘楚峰,曹阳,赵志河.大鼠实验性牙移动牙周组织Ⅰ型胶原的表达变化[J].广东牙病防治,2007,15(9):402-405.
[2]孙新华,朱宪春,徐成伟等.弱激光照射对兔牙移动速度及骨改建影响的实验研究[J].华西口腔医学杂志,2001,19(5):290-293.
[3]康祖铭,李春梅,石君等.旋转脉动磁场对兔正畸牙槽骨改建的影响[J].吉首大学学报(自然科学版).2010,31(2):108-110.
[4]廖建宏.超声波对正畸牙移动过程中牙龈血流量影响的临床研究[J].临床口腔医学杂志,2006,22(1):41-42.
[5]刘畅,孙新华,陈远萍等.局部应用二磷酸盐对鼠正畸牙移动影响的研究[J].中华口腔医学杂志,2002,37(4):290-293.
[6] Guanghong Han,Yuanping Chen,Jianhua Hou,et al. Effects of simvastatin on relapse and remodeling of periodontal tissues after tooth movement in rats [J]. American Journal of Orthodontics and Dentofacial Orthopedics,2010, 138, (5):550e1-550e7.
[7]沈刚,陈荣敬,刘侃.药物加速矫治牙移动的机理探讨[J].口腔医学,1993,13(1):47-48.
[8] Jeremy C. Karrasa, James R. Millerb, James S. Hodgesc.et al. Effect of alendronate on orthodontic tooth movement in rats[J]. American Journal of Orthodontics and Dentofacial Orthopedics,2009,136(6):843-847.
[9] Theodosia Bartzela, Jens C. Türp,Edith Motschall,et al. Medication effects on the rate of orthodontic tooth movement: A systematic literature review[J]. Am J Orthod Dentofacial Orthop, 2009,135(1):16-26.
[10]丁寅,陈华,徐如生.消炎痛对正畸牙齿移动影响的研究[J].口腔正畸学杂志,1994,1(2):80-81.
[11]冯江,万虎,吴耀禄.非甾体抗炎药致肝肾损害10例临床分析[J].陕西医学杂志,2000,29(2):118-119.
[12] J.J. Zahrowski.Bisphosphonate treatment: an orthodontic concern calling for a proactive approach [J], Am J Orthod Dentofacial ,2007: 311–320.
[13] Tokunaga T,Yano O,Kuramoto E,et a1.Synthetic oligonucleotides with particular base sequences from the eDNA encoding proteins of Mycobacerium bovis BCG induce intefereon and activate natural killer cells [J].Microbiol Immunol,1992,36(1):55-66.
[14] Han-A Kim,Hyun-Mi Ko,Hye-Won Ju,et al. CpG-ODN-based immunotherapy is effective in controlling the growth of metastasized tumor cells [J]. Cancer Letters, 2009,274 :160–164.
[15] Chun-sheng Liu ,Yun Sun,Yong-hua Hu,et al. Identification and analysis of the immune effects of CpG motifs that protect Japanese flounder (Paralichthys olivaceus) against bacterial infection [J]. Fish & Shellfish Immunology ,2010:1-7.
[16]李四堂,何知. CpG ODN与哮喘免疫治疗进展[J].江西医药,2009,44(10):1020-1022.
[17] HemmiH,TakeuchiO,KawaiT,et al.A Toll-like receptor recognizes bacterial DNA [J].Nature, 2000, 408(6813): 740-745.
[18]司兴奎,陈建红,张济培等. CpG寡脱氧核苷酸的免疫刺激特性及应用研究进展[J].动物医学进展,200,29(7):71-75.
[19] Krieg AM, Wu T, Weeratna R, et al. Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs[J. Proc Natl Acad Sci USA, 1998, 95(21): 12631-12636.
[20] Stunz LL, Lenert P, Peckham D, et al. Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells[J]. Eur J Immunol, 2002, 32(5): 1212-1222.
[21]王瑾,张王刚.CpG ODN序列结构特征对免疫活性影响的研究进展[J].细胞与分子免疫学杂志,2008,24(12):1219-1221.
[22]金伯泉.固有免疫中模式识别受体及其信号转导一当代免疫学中最伟大的发现之一[J].细胞与分子免疫学杂志,2006,22(1):1-3.
[23]钱旭波,蔡晓红. Toll样受体9及其配体研究进展[J].医学综述,2010,16(19):2886-2887.
[24] Akira S.TLR signaling.Curr Top Microbiol Immunol,2006,311:1.
[25]冯涛. TLR9的结构、功能及信号传导研究进展[J].国外医学免疫学分册,2005,28(2 ):72-76.
[26] Andor Pivarcsi.Toll-Like Receptor 9-Independent Suppression of Skin Inflammation by Oligonucleotides [J].Journal of Investigative Dermatology,2007,127: 746–748.
[27] Arash Ronaghy,Berent J.Prakken,Kenji Takabayashi,et al.Immunostimulatory DNA Sequences Influence the Course of Adjuvant Arthritis1 [J].The Journal ofImmunology,2002,168:51–56.
[28] Dennis Klinman,Hidekazu Shirota,Debra Tross,et al.Synthetic oligonucleotides as modulators of inflammation [J].J Leukoc Biol,2008,84(4):958–964.
[29] Weronika Rudnicka,Tomasz Burakowski,Ewa Warnawin.Functional TLR9 modulates bone marrow B cells from rheumatoid arthritis patients [J].Eur. J. Immunol,2009,39:211–1220.
[30]王凌,李大金.Toll样受体在成骨细胞和破骨细胞中的表达及作用[J].国外医学内分泌学分册,2005,25(5):330-332.
[31] Nemoto E, Honda T, Kanaya S,et al. Expression of functional Toll-like receptors and nucleotide-binding oligomerization domain proteins in murine cementoblasts and their upregulation during cell differentiation. J Periodont Res 2008; 43: 585–593.
[32]胡楠,何文喜,王玮等. TLR9在成牙本质细胞中的表达[J].口腔医学研究,2010,26(4):464-466.
[33] Wei Zou,Harry Schwartz,Stefan Endres,et al.CpG oligonucleotides: Novel regulators of osteoclast differentiation [J].FASEB J,2002,16:274–282.
[34]赵为公,韩学哲,刘淼等.富含CpG的脱氧核苷酸片段对破骨细胞形成的调节作用[J].第四军医大学学报,2004,25(15):1386-1388.
[35] Masako Yoshimatsu,Hideki Kitaura,et al.IL-12 inhibits TNF-αinduced osteoclasto- genesis via a T cell-independent mechanism in vivo [J].Bone,2009,45(5): 1010- 1016.
[36] Alla Amcheslavsky,Zvi Bar-Shavit.Interleukin (IL)-12 Mediates the Anti- Osteoclastogenic Activity of CpG- Oligodeoxynucleotides [J].Journal of Cellular Physiology,2006,207:244–250.
[37] Alla Amcheslavsky,Zvi Bar-Shavit.Toll-Like Receptor 9 Ligand Blocks Osteoclast Differentiation Through Induction of Phosphatase [J].J Bone Miner Res,2007,22: 1301–1310.
[38] Jae-Ho Chang a, Eun-Ju Chang c, Hong-Hee Kim c,et al.Enhanced inhibitory effects of a novel CpG motif on osteoclast differentiation via TREM-2 down–regulation [J].Biochemical and Biophysical Research Communications ,2009, 389:28–33.
[39] Wei Zou,Alla Amcheslavsky,and Zvi Bar-Shavit.CpG oligodeoxynucleotides modulate the osteoclastogenic activity of osteoblasts via toll-like receptor 9 [J].The Journal of Biological Chemistry,2003,278(19):16732-16740.
[40] Alla Amcheslavsky,Hiroaki Hemmi,Shizuo Akira,et al .Differential Contributionof Osteoclast- and Osteoblast-Lineage Cells to CpG-Oligodeoxynucleotide (CpG-ODN) Modulation of Osteoclastogenesis [J].J Bone Miner Res,2005,20:1692– 1699.
[41]申玉芹,孙新华,于丽等.不同CpG ODN对大鼠骨髓间充质干细胞增殖作用的研究[J].口腔医学研究,2009,25(6):723-725.
[42]申玉芹,孙新华,于丽等.小寡核苷酸对大鼠骨髓间充质干细胞向成骨细胞分化的影响[J].吉林大学学报(医学版),2010,36(2):336-339.
[43]申玉芹.寡核苷酸(ODN)促骨髓间充质干细胞向成骨细胞分化作用及机制研究[D].吉林:吉林大学口腔医学院,2010.
[44] Guang Yang,Min Wan,Yongsheng Zhang,te al. Inhibition of a C-rich oligodeoxynucleotide on activation of immune cells in vitro and enhancement of antibody response in mice[J]. mmunology, 2010,131, 501–512.
[45]杨光.富含胞嗜陡的脱氧寡核普酸对免疫反应的负调节作用[D].吉林,吉林大学白求恩医学院,2009
[46] King GJ,Keeling SD,McCoy EA,et al.Measuring dental drift and orthodontic tooth movement in response to various initial forces in adult rat [J].Am J Orthod Dentofacial Orthop,1991,99(5):456-465.
[47] YAMASAKI K, MIURA F,SUDA T. Prostaglandin as a mediator of bone resorption induced by experimental tooth movement in rats[J]. J Dent Res, 1980, 59:1635-1642.
[48]丁寅,陈华,徐如生.中药丹参加速正畸牙齿移动的研究[J].口腔医学,1995,15(3):120-121.
[49]华咏梅,王宏伟,牟福元.可溶性白细胞介素-1和肿瘤坏死因子受体对大鼠正畸牙移动影响的研究.华西口腔医学杂志,2008, 26(2):189-193.
[50] Kim TW,Yoshide Y,Yokoya K,et al.An ultrastructural study of the effects of bisphosphonate administration on osteoclastic bone resorption during relapse of experimentally moved rat molars.Am J Orthod Dentofac Orthop,1999,115:645-653.
[51]韩光红,陈远萍,侯建华等.辛伐他汀抑制正畸牙齿移动后复发距离的实验研究[J].现代口腔医学杂志,2006,20(6):621-623.
[52] Tokunaga T,Yano O,Kuramoto E,et a1.Synthetic oligonucleotides with particular base sequences from the eDNA encoding proteins of Mycobacerium bovis BCG induce intefereon and activate natural killer cells [J].Microbiol Immunol,1992,36(1): 55-66.
[53]任继玲.动物特异性CpG ODN的设计、筛选及对疫苗的增效作用[D].吉林:吉林大学白求恩医学院,2010.
[54] Krieg AM,Hartmann G,Yi AK.Mechanisms of action of CpG DNA[J].Curr Top Microbio Immunol,2000,247:l-21.
[55] Krieg.A.M,Yi A.K,Sehorr J.The role of CpG deoxynueleotides in DNA vaceine [J]. Trends. Mierobiol,1998,6:23-27.
[56] Kamstrup S,Verthelyi D,Klinman DM. Response of porcine peripheral blood mononuclear cells to CPG-containing oligodeognlileotides [J].Vet Microbiol,2001:78(4): 353-62.
[57] Hrtmann G,Krieg AM.Mechanism and function of a newly identified CPG DNA motif in human Primary B cells [J].J Immunol,2000,164:944-952.
[58] Hartmann G, Weeratna RD, Ballas ZK, Payette P, Blackwell S, Suparto I, et al. Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo [J] .J Immunol,2000 , 164(3):1617-1624.
[59] Mutwiri G, Pontarollo R, Babiuk S, et al. Biological activity of immunostimulatory CpG DNA motifs in domestic animals[J]. Vet Immunol Immunopathol, 2003,91(2):89-103.
[60] Nichani AK, Kaushik RS, Mena A, Popowych Y, Dent D, Townsend HG, et al. CpG oligodeoxynucleotide induction of antiviral effector molecules in sheep [J]. Cell Immunol,2004 ,227(1):24-37.
[61] Gunther H,Risini D.Delineation of a CpG phophorothioate Oligodeoxynueleo- tide for Activating Primate Immune Response In vitor and In vivo [J].The Joumal of Immunology. 2000,164,1617-1624.
[62]许洪林,王四清,王世峰.利用小鼠模型评价含5-GTC GTT-3特征序列的人CpG寡脱氧核苷酸免疫刺激活性[J].病毒学报.2001,17(l): 43-47.
[63]季颖,江志强.口腔黏膜给药系统研究进展[J].中国生化药物杂志,2003,24,(3):150-152.
[64]李丁,王健,侯惠民.口腔黏膜给药系统研究进展[J].中国医药工业杂志,2009,40,(4):303-307.
[65] Suna Wang,Qunying Han,Ni Zhang,et al. HBcAg18–27 epitope fused to HIV-Tat49–57 adjuvanted with CpG ODN induces immunotherapeutic effects in transgenic mice[J]. Immunology Letters,2010,127:143–149.
[66] Hui Zhang, Quan Gong , Jun-hua Li,et al. CpG ODN pretreatment attenuates concanavalin A-induced hepatitis in mice[J]. International Immunopharmaco- logy,2010, 10:79–85.
[67] Maria Pihlgren, Chantal Tougne, Nadine Schallert,et al. CpG-motifs enhance initial and sustained primary tetanus-specific antibody secreting cell responses in spleen and bone marrow, but are more effective in adult than in neonatal mice [J]. Vaccine, 2003,21:2492–2499.
[68] Arthur M Krieg. A possible cause of joint destruction in septic arthritis[J]. Arthritis Research,1999, 1(1):3-4.
[69]郭莹莹.CpG ODN在OVA诱导的哮喘小鼠模型中的治疗作用[D].吉林:吉林大学白求恩医学院,2010.
[70] Daniel E. Speiser, Danielle Liénard,Nathalie Rufer,et al. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleo- tide 7909 [J]. J Clin Invest. 2005, 115(3): 739–746.
[71] Molenkamp BG,van Leeuwen PA.Meijer S,et a1.Intradermal CpG-B activates both plasmaeytoid and myeloid dendritic cells in the sentinel lymph node of melanoma patients[J].Clin Cancer Res,2007,13(10):2961-2969.
[72] Krieg AM. CpG motifs in bacterial DNA and their immune effects [J]. Annu Rev Immunol, 2002,20:709-60.
[73] wilson Hg.Dar A,Napper SK.et a1.Immune mechanisms and therapeutic potential of CpG oligodeoxynucleotides[J].Int Rev Immunol,2006,25(3-4):183-213.
[74]宋光,张卓然.CpG寡核苷酸的安全性实验研究[J].中国微生态学杂志,2004,16 (6):321- 326.
[75] Hartmann G, Weeratna RD, Ballas ZK, Payette P, Blackwell S, Suparto I, et al. Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo. [J] J Immunol. 2000 Feb 1;164(3):1617-1624.
[76]何威,周佩军,沈周俊.新型的免疫佐剂:CpG寡聚脱氧核苷酸[J].中国临床医学,2008,15(5):673-676.
[77] Bourauel C, Freudenreich D, Vollmer D, et al. Simulation of orthodontic tooth movements. A comparison of numerical models[J]. J Orofac Orthop,1999, 60(2): 136-151.
[78] Zeuner RA, Ishii KJ, Lizak MJ, Gursel I, Yamada H, Klinman DM, et al.Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides [J]. Arthritis Rheum 2002;46:2219-24.
[79] Li Dong, Shu-ichi Ito, Ken J. Ishii,et al. Suppressive Oligonucleotides Protect Against Collagen-Induced Arthritis in Mice [J]. ARTHRITIS & RHEUMATISM , 2004, 50(5): 1686–1689.
[80] Brudvik P , Rygh P. The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament [J] . Eur J Orthod ,1993 ,15 :2249- 2263.
[81] Thomas MJ, Robert L. Orthodontics-Current principle and techniques[J].Orthod Waves. 1999,58:416-427.
[82] Nonglak P. Sombunthama, Siriwan Songwattanab, Phumvuth Atthakornc, Sumon Jungudomjaroend and Busaba Panyarachune. Early tooth movement with a clear plastic appliance in rats [J].American Journal of Orthodontics and Dentofacial Orthopedics,2009, 136( 1): 75-82.
[83]郭力嘉.正畸牙齿移动过程中破骨细胞表达的动物实验研究[D].硕士.辽宁:大连医科大学,2009.
[84] Zhang Y H, Heulsmann A, TondraviM M, et al. Tumor necrosis factor-alpha ( TNF) stimulates RANKL-induced osteoclastogenesis via coup ling of TNF type I recep tor and RANK signaling pathways [ J ]. J Biol Chem, 2001, 276 (1) : 563-568.
[85] Wada T, Nakashima T, Hiroshi N, et al. RANKL-RANK signaling in osteoclastogenesis and bone disease [ J ]. TrendsMolMed,2006, 12 (1) : 17-25.
[86]刘长庚,凌天牖,黄生高.OPG/RANKL /RANK系统及其临床应用[J].国际病理科学与临床杂志,2007,27(6):534-538.
[87]郝鹏杰,李建昌,王霄立等.不同浓度1,25-二羟基维生素D3对大鼠正畸牙移动速度的影响[J].广东牙病防治,2008,16(8):348-350.
[88] Lee WC.Experimental study of the effect of prostaglandin administration on the tooth movement with particular emphasis on the relationship to the method of PGE1 administration [J].Am J Orthod Dentofacial Orthop,1990,98:231-241.
[89]裘松波,杨健,谭颖徽.核因子-κB受体活化因子配体在大鼠正畸牙压力侧牙周组织中的表达[J].牙体牙髓牙周病学杂志,2005,15(2):76-79.
[90] Yamauchi, E.P. Katz and G.L. Mechanic, Intermolecular crosslinking and stereospecific molecular packing in type I collagen fibrils of the periodontal ligament [J].Biochemistry,1986, 25: 4907–4913.
[91] Sodek and J.M. Ferrier, Collagen remodelling in rat periodontal tissues: compensation for precursor reutilization confirms rapid turnover of collagen [J].Coll. Relat, 1988,1 : 11–21.
[92] Sutherland MSK, Rao L G, Muzaffar SA , et al. Age2 dependent expression of osteoblastic phenotypic markers in normal human osteoblasts cultured Long term in the presence of dexamethasone [J] . Osteo porosis Int , 1995 , 5 :335-343.
[93]王海彬,何伟,袁浩.成骨细胞和Ⅰ型胶原.中国中医骨伤科杂志,2003,11(3):56-58.
[94] Scheven BA, Hamilton NJ, Farquharson C, et al. Immunohistochemical localization of native and denatured collagen typesⅠa ndⅡin fetal and adult rat long bones [J].Bone, 1988,9(6):407-14.
[95] NAKAGAWAM, KUKITAT, NAKASIMA A, et al. Expression of the type I collagen gene in rat periodontal ligament during tooth movement as revealed by in situ hybridization [J]. ArchOral Biol, 1994,39(4):289-294.
[96] BUMANN A, CARVALHO R S, SCHWARZER C L, et al. Collagen synthesis from human PDL cells following orthodontic tooth movement [J].Eur J Orthod, 1997,19(1):29-37.
[97] FUKUI T, YAMANEA, KOMATSUK, et al. Restoration of mechanical strength and morphological features of the periodontal ligament following orthodontic retention in the rat mandibular first molar [J]. Eur J Orthod,2003,25(2):167-174.
[98]刘楚峰,曹阳,赵志河.大鼠实验性牙移动牙周组织Ⅰ型胶原的表达变化[J].广东牙病防治,2007,15(9):402-405.