免疫球蛋白IgY对牙龈卟啉单胞菌诱导的牙周炎大鼠模型的影响
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摘要
研究了免疫球蛋白(IgY)通过抑制P.gingivalis的生长繁殖治疗实验性大鼠牙周炎的可行性.用医用丝线结扎上颌第二磨牙,并涂抹P.gingivalis的方法建立大鼠牙周炎模型.建模成功的大鼠随机分成对照组、高剂量IgY组和低剂量IgY组,每组8只.给药28 d后,测量各组大鼠的牙龈指数(GI),菌斑指数(PI)和探诊出血指数(BOP),以及血液中IL-6和TNF-α含量,并进行X-射线影像和组织学观察.与对照组相比,IgY治疗组GI、PI和BOP指标明显好转,IL-6和TNF-α含量显著降低,X-射线影像可见牙间隙明显缩小,组织学观察牙周纤维排列整齐,极少量炎细胞浸润,牙槽嵴无吸收,牙槽骨骨质增加.特异性IgY能够治疗P.gingivalis诱导的大鼠牙周炎.
This study evaluates the therapeutic effects of egg yolk Immunoglobulin(IgY)on periodontitis in an established rat periodontitis model through the growth inhibition of Porphyromonas gingivalis. Experimental periodontitis was induced in mice by ligation of their second molar with medical thread and oral infection with Porphyromonas gingivalis.Periodontitis rats were randomly divided into control, high-dose, and low-dose groups.Each group was comprised of eight rats. The gingival index(GI), plaque index(PI), and bleeding on probing(BOP) were evaluated, the levels of IL-6 and TNF-a were examined,and an X-ray image and histomorphological section were observed after 28 days. Compared with the control, the scores for PI, GI, and BOP and the levels of IL-6 and TNF-a were significantly decreased in the IgY-treated groups. X-ray images showed that the tooth gap narrowed considerably. Pathological observation, furthermore, showed that periodontal fibers were neatly arranged, a small amount of inflammatory cells were infiltrated, the alveolar ridge was not absorbed, and alveolar bone increased. In conclusion, specific IgY can treat periodontitis induced by P. gingivalis in an established rat periodontitis model.
This study evaluates the therapeutic effects of egg yolk Immunoglobulin(IgY)on periodontitis in an established rat periodontitis model through the growth inhibition of Porphyromonas gingivalis. Experimental periodontitis was induced in mice by ligation of their second molar with medical thread and oral infection with Porphyromonas gingivalis.Periodontitis rats were randomly divided into control, high-dose, and low-dose groups.Each group was comprised of eight rats. The gingival index(GI), plaque index(PI), and bleeding on probing(BOP) were evaluated, the levels of IL-6 and TNF-a were examined,and an X-ray image and histomorphological section were observed after 28 days. Compared with the control, the scores for PI, GI, and BOP and the levels of IL-6 and TNF-a were significantly decreased in the IgY-treated groups. X-ray images showed that the tooth gap narrowed considerably. Pathological observation, furthermore, showed that periodontal fibers were neatly arranged, a small amount of inflammatory cells were infiltrated, the alveolar ridge was not absorbed, and alveolar bone increased. In conclusion, specific IgY can treat periodontitis induced by P. gingivalis in an established rat periodontitis model.
引文
[1]孟焕新.牙周病学[M]. 3版.北京:人民卫生出版社,2008:100-101.
[2]SILVA N, ABUSLEME L, BRAVO D, et al. Host response mechanisms in periodontal diseases[J]. Journal of Applied Oral Science, 2015, 23(3):329-355.
[3]HAJISHENGALLISA G. Immunomicrobial pathogenesis of periodontitis:keystones, pathobionts, and host response[J]. Trends in Immunology, 2014, 35(1):3-11.
[4]HAJISHENGALLISA G, MAEKAWAA T, ABE T, et al. Complement involvement in periodontitis:Molecular mechanisms and rational therapeutic approaches[J]. Advances in Experimental Medicine and Biology, 2015, 865:57-74.
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[6]KE XJ, LEI L, LI H, et al. Manipulation of necroptosis by Porphyromonas gingivalis inperiodontitis development[J]. Molecular Immunology, 2016, 77:8-13.
[7] MULLER S, SCHUBERT A, ZAJAC J, et al. IgY antibodies in human nutrition for disease prevention[J].Nutrition Journal, 2015, 14:109.
[8]江千舟,樊明文,李宇红,等.鸡蛋黄抗体IgY的急、慢性毒性实验[J].牙体牙髓牙周病学杂志,2001, 11(6):389-391.
[9]YOKOYAMA K, SUGANO N, RAHMAN AK, et al. Activity of anti-Porphyromonas gingivalis egg yolk antibody against gingipains in vitro. Oral Microbiology and immunology, 2007, 22(5):352-355.
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[11] TEZUKA A, HAMAJIMA S, HATTA H, et al. Inhibition of Porphyromonas gingivalis hemagglutinating activity by IgY against a truncated HagA[J]. Journal of Oral Science, 2006, 48(4):227-232.
[12] HUANG S G, HUANG Q L, HUANG B, et al. The effect of Scutellaria baicalensis Georgi on immune response in mouse model of experimental periodontitis[J]. Journal of Dental Sciences, 2013, 8(4):405-411.
[13]孙继军,王栋,王爱芹.实验性牙周炎大鼠模型的建立[J].中国组织工程研究,2012, 16(37):6867-6870.
[14] SHOFIQUR R, SA V N, FAUSTINO C, et al. Oral passive IgY based immune therapeutics[J]. Human Vaccines&Immunotherapeutics, 2013, 9(5):1039-1048.
[15]姜大川,徐燕.抗牙龈卟啉单胞菌蛋黄免疫球蛋白免疫防治牙周炎[J].国际口腔医学杂志,2009, 36(6):682-684.
[16] LI X Y, LIU H, XU Y P, et al. Chicken egg yolk antibody(IgY)controls Solobacterium moorei under in vitro and in vivo conditions[J]. Applied Biochemistry and Biotechnology, 2012, 168(6):1448-1458.
[17]王芳,周喻,许啸晨,等.基于Box Behnken响应面法优化口腔模拟环境IgY抑制牙龈卟啉单胞菌增殖[J].微生物学通报,2017, 44(11):2689-2697.
[18] JAIN S, DARYEAU R P. Contribution of porphyromonas gingivalis lipopolysaccharide to periodontitis[J].Periodontology 2000, 2010, 54(1):53-70.
[19] HAJISHENGALLIS G. Periodontitis:From microbial immune subversion to systemic inflammation[J]. Nature Reviews Immunology, 2015, 15(1):30-44.
[20]刘迪,杨丕山,胡德渝,等.盐酸米诺环索脂质体控释凝胶改善大鼠实验性牙周炎的作用评价[J].华西口腔医学杂志,2013,31(6):592-596.
[21]孙俊毅,朱春晖,刘瑾,等.盐酸小檗碱调节大鼠实验性牙周炎牙龈组织MMPs/TIMP表达变化及其机制[J].西安交通大学学报(医学版),2016, 37(4):551-555.
[22] DE ARAUJO A A, DE CASTRO BRITO G A, DE SOUZA ARAUJO L, et al. Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis[J]. Plos One, 2017, 12(8):e0183506.
[23]刘赟、王丹,甄玉红,等.中间普氏菌特异性卵黄抗体治疗大鼠牙龈炎的研究[J].口腔医学研究,2012, 28(5):413-416.
[24] HOU Y Y, ZHEN Y H, WANG D, et al. Protective effect of an egg yolk-derived immunoglobulin(IgY)against Prevotella intermedia-mediated gingivitis[J]. Journal of Applied Microbiology, 2013, 116, 1020-1027.
[25]吴亚菲,赵川江,张静仪,等.牙龈沟液中白细胞介素-6含量与牙周炎关系的研究[J].华西医大学报,2000, 31(4):494-496.
[26]吴婷.冠心病伴牙周炎患者血脂、血清炎症因子的相关研究[D].济南:山东大学,2010.
[2]SILVA N, ABUSLEME L, BRAVO D, et al. Host response mechanisms in periodontal diseases[J]. Journal of Applied Oral Science, 2015, 23(3):329-355.
[3]HAJISHENGALLISA G. Immunomicrobial pathogenesis of periodontitis:keystones, pathobionts, and host response[J]. Trends in Immunology, 2014, 35(1):3-11.
[4]HAJISHENGALLISA G, MAEKAWAA T, ABE T, et al. Complement involvement in periodontitis:Molecular mechanisms and rational therapeutic approaches[J]. Advances in Experimental Medicine and Biology, 2015, 865:57-74.
[5]齐小秋.第三次全国口腔健康流行病学调査报告[M].北京:人民卫生出版社,2008:78-82.
[6]KE XJ, LEI L, LI H, et al. Manipulation of necroptosis by Porphyromonas gingivalis inperiodontitis development[J]. Molecular Immunology, 2016, 77:8-13.
[7] MULLER S, SCHUBERT A, ZAJAC J, et al. IgY antibodies in human nutrition for disease prevention[J].Nutrition Journal, 2015, 14:109.
[8]江千舟,樊明文,李宇红,等.鸡蛋黄抗体IgY的急、慢性毒性实验[J].牙体牙髓牙周病学杂志,2001, 11(6):389-391.
[9]YOKOYAMA K, SUGANO N, RAHMAN AK, et al. Activity of anti-Porphyromonas gingivalis egg yolk antibody against gingipains in vitro. Oral Microbiology and immunology, 2007, 22(5):352-355.
[10] HAMAJIMA S, MARUYAMA M, HIJIYA T, et al. Egg yolk-derived immunoglobulin(IgY)against Porphyromonas gingivalis 40-kDa outer membrane protein inhibits coaggregation activity[J]. Archives of Oral Biology,2007, 52:697-704.
[11] TEZUKA A, HAMAJIMA S, HATTA H, et al. Inhibition of Porphyromonas gingivalis hemagglutinating activity by IgY against a truncated HagA[J]. Journal of Oral Science, 2006, 48(4):227-232.
[12] HUANG S G, HUANG Q L, HUANG B, et al. The effect of Scutellaria baicalensis Georgi on immune response in mouse model of experimental periodontitis[J]. Journal of Dental Sciences, 2013, 8(4):405-411.
[13]孙继军,王栋,王爱芹.实验性牙周炎大鼠模型的建立[J].中国组织工程研究,2012, 16(37):6867-6870.
[14] SHOFIQUR R, SA V N, FAUSTINO C, et al. Oral passive IgY based immune therapeutics[J]. Human Vaccines&Immunotherapeutics, 2013, 9(5):1039-1048.
[15]姜大川,徐燕.抗牙龈卟啉单胞菌蛋黄免疫球蛋白免疫防治牙周炎[J].国际口腔医学杂志,2009, 36(6):682-684.
[16] LI X Y, LIU H, XU Y P, et al. Chicken egg yolk antibody(IgY)controls Solobacterium moorei under in vitro and in vivo conditions[J]. Applied Biochemistry and Biotechnology, 2012, 168(6):1448-1458.
[17]王芳,周喻,许啸晨,等.基于Box Behnken响应面法优化口腔模拟环境IgY抑制牙龈卟啉单胞菌增殖[J].微生物学通报,2017, 44(11):2689-2697.
[18] JAIN S, DARYEAU R P. Contribution of porphyromonas gingivalis lipopolysaccharide to periodontitis[J].Periodontology 2000, 2010, 54(1):53-70.
[19] HAJISHENGALLIS G. Periodontitis:From microbial immune subversion to systemic inflammation[J]. Nature Reviews Immunology, 2015, 15(1):30-44.
[20]刘迪,杨丕山,胡德渝,等.盐酸米诺环索脂质体控释凝胶改善大鼠实验性牙周炎的作用评价[J].华西口腔医学杂志,2013,31(6):592-596.
[21]孙俊毅,朱春晖,刘瑾,等.盐酸小檗碱调节大鼠实验性牙周炎牙龈组织MMPs/TIMP表达变化及其机制[J].西安交通大学学报(医学版),2016, 37(4):551-555.
[22] DE ARAUJO A A, DE CASTRO BRITO G A, DE SOUZA ARAUJO L, et al. Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis[J]. Plos One, 2017, 12(8):e0183506.
[23]刘赟、王丹,甄玉红,等.中间普氏菌特异性卵黄抗体治疗大鼠牙龈炎的研究[J].口腔医学研究,2012, 28(5):413-416.
[24] HOU Y Y, ZHEN Y H, WANG D, et al. Protective effect of an egg yolk-derived immunoglobulin(IgY)against Prevotella intermedia-mediated gingivitis[J]. Journal of Applied Microbiology, 2013, 116, 1020-1027.
[25]吴亚菲,赵川江,张静仪,等.牙龈沟液中白细胞介素-6含量与牙周炎关系的研究[J].华西医大学报,2000, 31(4):494-496.
[26]吴婷.冠心病伴牙周炎患者血脂、血清炎症因子的相关研究[D].济南:山东大学,2010.