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环孢素、硝苯地平和苯妥英对猴子牙龈肌成纤维细胞转分化的影响。

Effects of cyclosporin, nifedipine and phenytoin on gingival myofibroblast transdifferentiation in monkeys.

作者信息

Kanno Claudia Misue, Oliveira Jose Americo de, Ervolino Edilson, Soubhia Ana Maria Pires

机构信息

Univ. Estadual Paulista, Faculdade de Odontologia, Departamento de Emergência, Araçatuba, São Paulo, Brasil.

Univ. Estadual Paulista, Faculdade de Odontologia, Departamento de Ciências Básicas, Araçatuba, São Paulo, Brasil.

出版信息

J Appl Oral Sci. 2018 Nov 8;27:e20180135. doi: 10.1590/1678-7757-2018-0135.

DOI:10.1590/1678-7757-2018-0135
PMID:30427475
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6223785/
Abstract

OBJECTIVE

Myofibroblasts have been associated with the development of several pathologic fibrotic conditions. This longitudinal study aims to assess the proliferative and antiapoptotic effects of cyclosporin, nifedipine and phenytoin on gingival connective tissue cells of nonhuman primate, as well as to analyze a possible role of myofibroblasts in gingival overgrowth.

MATERIALS AND METHODS

Gingival samples from the right superior canine area were obtained from 12 male monkeys ( Sapajus spp ) to comprise the control group. After one week, the animals were randomly assigned to three groups, which received daily oral doses of cyclosporin, nifedipine or phenytoin for 120 days. Gingival samples were collected from the left superior canine area of two animals of each group at 52 and 120 days. Histological sections were stained with hematoxylin and eosin, and immunoreacted against α-SMA, Ki- 67 and bcl-2.

RESULTS

α-SMA immunoreaction was negative in the control and experimental groups. Similarly, no difference between groups concerning immunostaining against Ki-67 and bcl-2 was observed in connective tissue cells.

CONCLUSION

Based on this methodology, it may be concluded that gingival overgrowths induced by cyclosporin, nifedipine and phenytoin are not associated with neither myofibroblast transdifferentiation, proliferation nor apoptosis of gingival connective cells in monkeys.

摘要

目的

肌成纤维细胞与多种病理性纤维化疾病的发展有关。这项纵向研究旨在评估环孢素、硝苯地平和苯妥英对非人灵长类动物牙龈结缔组织细胞的增殖和抗凋亡作用,并分析肌成纤维细胞在牙龈过度生长中可能发挥的作用。

材料与方法

从12只雄性猴子(僧面猴属)的右上犬齿区域获取牙龈样本,组成对照组。一周后,将动物随机分为三组,分别每日口服环孢素、硝苯地平或苯妥英,持续120天。在第52天和第120天,从每组的两只动物的左上犬齿区域采集牙龈样本。组织学切片用苏木精和伊红染色,并与α-SMA、Ki-67和bcl-2进行免疫反应。

结果

对照组和实验组的α-SMA免疫反应均为阴性。同样,在结缔组织细胞中,各组之间针对Ki-67和bcl-2的免疫染色也未观察到差异。

结论

基于该方法,可以得出结论,环孢素、硝苯地平和苯妥英诱导的牙龈过度生长与猴子牙龈结缔组织细胞的肌成纤维细胞转分化、增殖或凋亡均无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/6620296ce8d3/1678-7765-jaos-27-e20180135-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/54bbd845d037/1678-7765-jaos-27-e20180135-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/7d4aca4514c1/1678-7765-jaos-27-e20180135-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/674465407e27/1678-7765-jaos-27-e20180135-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/6620296ce8d3/1678-7765-jaos-27-e20180135-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/54bbd845d037/1678-7765-jaos-27-e20180135-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/7d4aca4514c1/1678-7765-jaos-27-e20180135-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/674465407e27/1678-7765-jaos-27-e20180135-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd9/6223785/6620296ce8d3/1678-7765-jaos-27-e20180135-gf04.jpg

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本文引用的文献

1
Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases.内皮-间充质转化(EndoMT)在人类纤维化疾病发病机制中的作用
J Clin Med. 2016 Apr 11;5(4):45. doi: 10.3390/jcm5040045.
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Cyclosporine A promotes cell proliferation, collagen and α-smooth muscle actin expressions in rat gingival fibroblasts by Smad3 activation and miR-29b suppression.环孢素A通过激活Smad3和抑制miR-29b促进大鼠牙龈成纤维细胞的增殖、胶原蛋白和α-平滑肌肌动蛋白的表达。
J Periodontal Res. 2016 Dec;51(6):735-747. doi: 10.1111/jre.12350. Epub 2016 Jan 6.
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Human gingival fibroblasts display a non-fibrotic phenotype distinct from skin fibroblasts in three-dimensional cultures.
在三维培养中,人牙龈成纤维细胞表现出与皮肤成纤维细胞不同的非纤维化表型。
PLoS One. 2014 Mar 7;9(3):e90715. doi: 10.1371/journal.pone.0090715. eCollection 2014.
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Understanding the origin, activation and regulation of matrix-producing myofibroblasts for treatment of fibrotic disease.理解产生细胞外基质的肌成纤维细胞的起源、激活和调控,以治疗纤维化疾病。
J Pathol. 2013 Nov;231(3):273-89. doi: 10.1002/path.4253.
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Requirement for active glycogen synthase kinase-3β in TGF-β1 upregulation of connective tissue growth factor (CCN2/CTGF) levels in human gingival fibroblasts.TGF-β1 上调人牙龈成纤维细胞结缔组织生长因子(CCN2/CTGF)水平需要活性糖原合酶激酶-3β。
Am J Physiol Cell Physiol. 2013 Sep 15;305(6):C581-90. doi: 10.1152/ajpcell.00032.2013. Epub 2013 Jul 3.
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Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and inflammation in cyclosporine A-induced gingival enlargement: a pilot in vitro study using a three-dimensional model of the human oral mucosa.基质金属蛋白酶、基质金属蛋白酶组织抑制剂与环孢素 A 诱导的牙龈增生中的炎症:采用人口腔黏膜三维模型的初步体外研究。
J Periodontol. 2013 May;84(5):634-40. doi: 10.1902/jop.2012.120224. Epub 2012 Aug 30.
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Cyclosporin A-induced gingival overgrowth is not associated with myofibroblast transdifferentiation.环孢素 A 诱导的牙龈过度生长与肌成纤维细胞转分化无关。
Braz Oral Res. 2010 Apr-Jun;24(2):182-8. doi: 10.1590/s1806-83242010000200010.
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