羧甲基壳聚糖促牙周组织再生的毒理学研究
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摘要
目的:研究羧甲基壳聚糖应用于牙周组织的安全性。
     方法:将32只昆明小鼠随机分为4组(每组8只),A为空白对照组,B为腹腔注射环磷酰胺阳性对照组,C、D为羧甲基壳聚糖梯度实验组,在手术骨缺损区置入梯度剂量的羧甲基壳聚糖。术后4周处死动物,应用彗星实验、嗜多染红细胞微核实验计算彗星尾数和微核率并进行统计学分析;收集牙周组织标本进行组织学观察。
     结果:A组、C组、D组间红细胞微核率及彗星尾数无显著差异(P>0.05),且C组与D组间亦无统计学差异(P>0.05),而B组的红细胞微核率及彗星尾数远高于其余3组(P<0.01)。术后4周C、D组骨缺损区可见少量新骨形成,A组未见新骨形成。
     结论:羧甲基壳聚糖在该毒理学实验中未显示毒性结果,提示牙周组织局部应用羧甲基壳聚糖安全可靠;并具有促进牙周骨组织再生的作用。
Objective:To study the safety of N,0-Carboxymethy chitosan using in periodontal regeneration.
     Method:32 mices were randomly divided into four groups with 8 rats in each group.Group A is negative group,B is positive group,C and D are different dose groups.N,0-Carboxymethy was implanted in mice's periodontal tissue of group C and D.Observed it's chronic and genetic toxicity by micronucleus,comet assay,tissue sections after 4 weeks.
     Results:The number of micronucleus rate and comet tail in group B are much higher than A,C,D(p<0.01);obvious difference wasn't exited between negative and test group(p>0.05),moreover,low group C and D also exited little difference(p>0.05).
     Conclusion:N,0-Carboxymethy chitosan doesn't exit toxicity in appling to periodontal tis
引文
1 岳树立主编.口腔内科学.第2版.北京:人民卫生出版社.1987:254.
    2 Hurzelar MB,Quinones CR,Caffesse RG et al.Guided periodontal tissue regeneration in class Ⅲ furcation defects following treatment with a synthetic bioabsorbable barrier.J Periodontol 1997 May;68(5):498-505.
    3 Somerman MJ,Ouyang HJ,Berry JE,et al.Evolution of periodontal regeneration:from the roots point of view[J].J periodont Res,1999,34:420-424.
    4 O'Neal R,Wang HL,Macneil RL et al.Cells and materials involved in guided tissue regeneration.Curr Opin Priodontal,1994:141-156.
    5 Corbet EF,Vaughan AJ,Kieser JB.The periodontally involved root surface.J Clin Periodontal,1993,20:402-410.
    6 Crespi R,Ugo C,Joseph E,et al.Periodontal tissue regeneration in Beagie dogs after laser theraphy[J].Laser Surge Med,1997,21:395-402.
    7 Kubota K,Yokota M,et al.Overview of effects of electrical stion on osteogenesis and alveolar bone[J].J periodontal,1995,66:2-6.
    8 吴织芬.牙周病学第二版.北京:人民卫生出版社,2002
    9 Ikada I.et.al.effect of chitosan hydrolysates on lipid absoption and on serum and liver lipid concentration in rats.J.Agr.Food chem.1993.41:431.
    10 Brown KM.Arthur JR.Selenium.selenoproteins and human health:a review[J].Public Health Nutr.2001,(4):593-599
    11 丘波,刘世清,杜予民等.壳聚糖膝关节腔注射疗法对兔骨关节炎关节软骨的影响.中华风湿学杂志,2004,8:591-595.
    12 李志勇,孙建宁.水合氯醛和戊巴比妥钠对SD大鼠麻醉效果的比较[J].四川动物,2008,27(2):299-302.
    13 刘静,于洪升.低剂量辐射对环磷酰胺所致小鼠DNA及遗传物质损伤的影响.青岛大学医学院学报,2008.44(1):44-47
    14 邢卫平,赵恒奎,姜宗荣,等.微核及微核试验在遗传毒理学中的应用.安徽预防遗传杂志,2002,8:317-332.
    15 Lekovic V,Camargo PM,Weinlaender M,et al.Acomparison between enamel matrix proteins,used alone or in combination with bovine porous bone mineral in the treatment of introbony barrier membranes periodontal defects in humans[J].J eriodontol,2000,71:1110-1116.
    16 Vijislav L,Paulo M,Camargo,et al.Conbination use of bovineporous bone mineral,enamel matrix periodontal defects in humans[J],J Periodontal,2001,72(5):583-589.
    17 Anton S,Giovanni C C,et al.Clinical evaluation of anenamel matrix protein derivative combined with a bioactive glass for the treatment of introbony periodontal defects in humans[J].J Periodontol,2002,73:40-408.
    18 赵征,张广耘,吴织芬,等动态观察bFGF和rhBMP对牙周膜细胞增殖的影响.现代口腔医学杂志,2003,17(4):299.
    19 林炎平.壳聚糖的结构、性质和应用.化学工程师,1998,68:33-35.
    20 Ebelein CG,Dunn RL,Progressive biomedical polymers.New York Plenum Press 1990,178-180
    21 王真,陈西广,郎刚华,等.甲壳质及其衍生物生理活性研究进展[J].海洋科学,2000,24(9):30-32.
    22 Denuziere A,Ferrier D,Damour D,et al.Chitosan-chondroitin sulfate and chitosan-hyaluronate polyelectrolyte complex:biological properties[J].Biomarerials,1998,19(14):1275-1285.
    23 Gaderod O,Smidsrod O,Skjak Braek G.Microcapsules of alginate-chitosan Ⅰ:Aquantitative study of the niteraction between alginate and chitosan[J].Biomaterials,1998,19(20):1815-1825.
    24 Lu JX,Prudhonmmeaux F,Meunier A,et al.Effects of chitosan on rat knee cartilages.Biomaterials,1999,20(20):1937-1994.
    25 Lee YM,Park Y J,Lee S J,et al.Tissue engineered bone formation using chitosan/tricalcium phosphate sponges[J].Periodontol,200,71(3):410-417.
    26 隋良朋,谢美慧,李建华等.氨基多糖羟基磷灰石复合人工骨充填拔牙窝临床观察.北京口腔医学.1996,4(4):164.
    27 杜梅.壳聚糖用药机制研究进展.南京军医学院学报,2000,22(3):184-188.
    28 Leroux L,Hatim Z,Fteche M.Effects of various adjuvants(lactic acid,glycerol,abdchitosan) on the injectability of a calcium phosphate cement.Bone 1999,25(2):31.
    29 Muzzarelli R,Biagini G,Pugnaloni A.Reconstruction for parodontal tissue with chitosan.Biomaterials,1989,10(9):598.
    30 张毅,庄昭霞,卢凤琦等.牙周引导组织再生壳聚糖膜的生物相容性研究.山东大学学报(医学版).2002,40(2)-115.
    31 Lester D,Jahnke K.Ceramic implants in otologic surgery.Am J Otol,1981,3:104.
    32 Stum PG,Hages SM.The effect of poly-N-acety lucosam inoglycan(chitosan) on osteogenesis in vitra.Periodontal 1996,67(11):1170
    33 Park YJ,Lee YM,Park SN,et al.Platelet derived growth factor releasing chitosan sponge for periodontal bonefegeneration.Biomaterials,2000,21(2):153-159.
    34 石玲等.壳聚糖的安全性研究.中国海洋药物杂志.2001.73(1):25-28.
    35 Soane.et al.Mechanism for the inhibition of fat digestion by chitosan and for the synergestic effect of ascorbate.Biosci.Biotechnol.Biochem.1995.59(5):786.
    36 吴晴斋等.甲壳素的毒理学研究.对小鼠致畸胎作用研究.中国生化药物杂志.1995.16(3):126-128.
    37 Ikada I.et.al.effect of chitosan hydrolysates on lipid absoption and on serum and liver lipid concentration in rats.J.Agr.Food chem.1993.41:431.
    38 王培昌,张宗玉,张建.彗星试验—一种DNA损伤水平与修复能力的测定方法.中华检验医学杂志,2006.7(29):651-652.
    39 邢卫平,赵恒奎,姜宗荣,等.微核及微核试验在遗传毒理学中的应用.安徽预防遗传杂志,2002,8:317-332.
    40 Soane RJ.,Frier M.,Perkins A C.,et al.Evaluation of the clearance characteristics of bioadhesive system in humans[J].Eur J Pharm Sci.,1996,4:23-31.
    [1]林炎平.壳聚糖的结构、性质利应用.化学工程师,1998,68:33-35.
    [2]陈伟,林友文,罗红斌,李柱米.羧甲基壳聚糖对钙离子的络合.福建医科大学学报,2000,6(2):163-165.
    [3]汪玉庭,刘玉红,张淑庭.甲壳素、壳聚糖的化学改性及其衍生物应用研究进展.功能高分子学报,2002,3.
    [4]王令冲,陈西广等.医用壳聚糖膜的性能及用途.中国海洋大学学报,2006,36(2):215-220.
    [5]杨越冬,周永国,等.应用于生物医学领域的化学改性壳聚糖.高分子通报,2006,2:52-54.
    [6]李牧.壳聚糖的性质及应用研究.科技信息,2007,20:52-54.
    [7]杨丕山,庄昭霞,孙钦峰,等.壳聚糖促进牙周再生的实验研究.山东医科大学学报,1998,36(3):204-206.
    [8]Zhang ZX,Lin ZY,Gao JE Biocompatibility of chitosan-car-boxymethylchiosan as membrane for periodontal guided tissue regeneration.Shanghai Kou Qiang Yi Xue,2003,30(5):443-453.
    [9]张毅,庄昭霞,等.牙周引导组织再生壳聚糖膜的生物相容性研究[J].山东大学学报,2002,40(2):115-117.
    [10]Ali F,Galen BS,Rebecca Z,et al.Chitosan supports the initial attachment and spreading of osteoblasts preferentially over fibroblasts[J].Biomaterials,2004,25:2075-2079.
    [11]卢风琦,曹宗顺,庄昭霞,等.壳聚糖膜的降解与生物相容性研究[J].生物学工程杂志,1998,15(2):183-185.
    [12]庄昭霞,林志勇,卢风琦,等.壳聚糖膜生物降解与组织反应的实验研究[J].口腔材料器械杂志,1997,6(4):178-180.
    [13]郑立,陈西广,刘万顺,等.羧甲基壳聚糖膜对皮肤呈纤维细胞相容性研究[J].生物化学与生物物理进展,2003,30(2):314-320.
    [14]曹宗顺,卢风琦.药用壳聚糖生物降解膜的研制[J].中国医药工业杂志,1996,27(1):14-16.
    [15]Nojima N,Kobayashi M,Takahashi N,et al.Fibroblastic cells derived from bovine periodontal ligaments have the phenotypes of osteoblasts.J periodontal Res,1990,25:179-185.
    [16]吴勇,王勤涛,吴织芬,袁乃梅.壳聚糖膜对人牙周膜细胞体外增殖的影响.口腔医学,2004,24(4):206-208.
    [17]张明珠,段开文,欧炯光.壳聚糖用于口腔疾病治疗中的研究现状.口腔材料器械杂志,2005,14(3):143-145.
    [18]Hamano T,Ghiba D,Teramoto A,et al.Effect of polyelectrolyte complex(PEC) on human periodontal ligament fibroblast(HPLF) function in the presence of glucocorticoids.J Biomater Sci Polym ED,1998,9(9):985-1000.
    [19]Muzzarelli R,Baldassarre Ⅴ,Conti F,et al.Biological activity of chitosan:ultrastructural study[J].Biomaterials,1988,9(3):247-252.
    [20]Mori T,Okumura M,Marsuurra M,et al.Effects of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro[J].Biomaterials,1997,18(13):947-951.
    [21]曹采方主编.牙周病学.第二版,2003:35.
    [22]夏文水,等.无锡轻工大学学报,1996,15(4):297.
    [23]郑连英,朱江峰,孙昆山.壳聚糖的抗菌性能研究.材料科学与工程,2000,18(2):22-24.
    [24]Keisuke U,ENO,et al[J].Adv.in Chitin Sci 1997,2:102.
    [25]Y.Shin,et al[J].Adv.in Chitin Sci 1997,2:890.
    [26]唐涛,薛毅,信玉华,谭巨莲.羟甲基壳聚糖对牙周炎优势厌氧菌抑菌性能评价.牙体牙髓牙周病学杂志,2004,14(10):587.
    [27]张澄波.壳聚糖对巨噬细胞精氨酸酶活性的影响[J].首都医学院学报,1992,13(3):234.
    [28]Sturm PG,Hayes SM.The effect of poly-N-Acetyl lucosaminoglycan(chitosan) on osteogenesis in vitro.J periodontal,1996,67(11 ):1170-1175.
    [29]Park Y J,Lee YM,Park SN,et al.Platelet derived growth factor releasing chitosan sponge for periodontal bonefegeneration.Biomaterials,2000,21(2):153-159.
    [30]夏文水,陈洁.甲壳素和壳聚糖的化学改性及其应用[J].无锡轻工业学院学报,1994,13(2):162-165.
    [31]马亚妮.壳质、壳聚糖与体育运动[J].体育科学,1999,19(3):80-83.
    [32]Ueno Hiroshi.Topical formulations and wound healing applications of chitosan.ADVANCED DRUG DELIVERY REVIEW,2001,52(2):105-116.
    [33]汤朝辉,侯春林.儿丁糖和透明质酸钠对人体表皮细胞增殖的影响[J].中华创伤杂志,2003,19(6):368-369.
    [34]曹采方主编.牙周病学.第二版,2003:194.
    [35]段开文,谭葆春,史明,吴恩格,张明珠.壳聚糖符合药膜的研制和试验研究.实用口腔医学杂志,2005,910:102-105.
    [36]卢凤岐,曹宗顺.明胶壳聚糖混合膜的制备与性质[J].生物医学工程杂志,1998,15(4):323.
    [37]Shuji N,Andrady A L.Permeability of vitamin B-12 in chitosan membranes,Effect of crosslinking and blending with poly(vinyl alcohol) on permeability[J].Journal of Applied Polyram Science,1992,44:17-28.
    [38]罗华丽,鲁在君.壳聚糖作为药物缓释载体的研究进展[J].高分子通报,2006,7:25-30.
    [39]蒋新宁,周春山,邓晔.壳聚糖载药微球的研制[J].常德师范学院学报,2003,15(1):36-39.
    [40]Hejazi R,Amiji M.Int J Pharm,2004,272:99-108.
    [41]Makarand VR,Anandwardhan AH,Sujata VB,et al.J Control Rel,2000,68:23-30.
    [42]Perugini P,Genta I,Conti B,et al.Periodontal delivery of ipriflavone:new chitosan/PLGA film delivery system for a lipophilic drug.Int J Pham,2003,252(1-2):1-9.
    [43]Kelly HM,Deasy PB,Ziaka E,et al.Formulation and preliminary in vivo dog studies of a novel drug delivery system for the treatment of periodontitis.Int J Pham,2004,274(1-2):167-183.
    [44]Sano H,Shibasakik,Matsukabo T,et al.Effect of chitosan rinsing on reduction of dental plague formation.Bull Takya Dent Coll,2003,44(1):9-16.
    [45]Choi BK,Kim KY,Yoo YJ,et al.In vitro antimicrobial activity of a chitooligosaccharide mixture against Actinobacillus actinomycetemcomitans and Streptococcus mutans.Int J Antimicrob Agents,2001,18(6):553-557.
    [46]Taris R,Muzzarelli RA,Guzman CA,et al.Inhibition of Streptococcus mutans adsorption to hydroxyapatite by low-molecular-weight chitosans J Dent Res,1997,76(2):665-672.
    [47]Ito M,Ban A,Ishihara M.Anti-ulcer effect of chitin and chitosan,healthy focus,in rats.J Pharmacol,2000,82(3):218-225.
    [48]刘瑾,唐梓进.羧甲基壳聚糖对口腔链球菌和口腔乳酸杆菌的抑制作用.南京师大学报,1999,22(4):73-76.
    [49]刘晓勇,李玉晶,赵宝荣.用甲壳胺直接盖髓的实验研究[J].现代口腔医学杂志,2001,15(50):336-337.
    [50]谭葆春.壳聚糖口腔符合药膜的研制及实验研究.昆明医学院硕士研究生学位论文,2003,6.
    [51]Olsen R,Schwartzmiller D,Weppner W,et al.Biomedical applications of chitin and its an antioxidant agent in fenestration defects 82~(nd)Annual meeting of NOF,Naantali-Finland,Abstract Book,1999,#83.
    [52]张文涛,卢世壁,王继芳,等.组织工程软骨移植修复兔类膝关节软骨缺损.中华外科杂志,1998,36:591.
    [53]Tsai GJ,Su WH.Antibacterial activity of shrimp chitosan against Escherichia coli.J Food Prot,1999,62(3):239-248.
    [54]Muzzarelli R,Filippini O,Tails R,et al.Antimicrobial properties of N-carboxyhuty 1chitosan.Antimicrob Agents chemother,1990,34(10):2019-2023.
    [55]刘瑾,唐梓进,羧甲基壳聚糖对口腔链球菌和口腔乳酸杆菌的抑制作用.南京师大学报,1999,22(4)73-76.

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