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罗红霉素下调转化生长因子β2 的表达,减少环孢素诱导的大鼠牙龈过度增生:一项实验研究。

Down-regulation of transforming growth factor beta-2 expression is associated with the reduction of cyclosporin induced gingival overgrowth in rats treated with roxithromycin: an experimental study.

机构信息

Department of Clinical Dental, Federal University of Juiz de Fora/UFJF - Juiz de Fora/Brazil, Dom André Arcoverde Foundation, Valença, Brazil.

出版信息

BMC Oral Health. 2009 Dec 8;9:33. doi: 10.1186/1472-6831-9-33.

DOI:10.1186/1472-6831-9-33
PMID:19995419
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2802586/
Abstract

BACKGROUND

Gingival overgrowth (GO) is a common side effect of the chronic use of cyclosporine (CsA), an immunosuppressant widely used to prevent rejection in transplant patients. Recent studies have reported elevated levels of specific cytokines in gingival overgrowth tissue, particularly TGF-beta, suggesting that this growth factor plays a role in the accumulation of extracellular matrix materials. The effectiveness of azithromycin, a macrolide antibiotic, in the regression of this undesirable side effect has also been demonstrated.

METHODS

In this study, we created an experimental model for assessing the therapeutic effect of roxithromycin in GO and the expression of transforming growth factor beta (TGF-beta2) through immunohistochemistry. We used four groups of rats totaling 32 individuals. GO was induced during five weeks and drug treatment was given on the 6th week as follows: group 1 received saline; group 2 received CsA and was treated with saline on the 6th week; group 3 received CsA and, on the 6th week, ampicilin; and group 4 received CsA during 5 weeks and, on the 6th week, was treated with roxithromycin.

RESULTS

The results demonstrated that roxithromycin treatment was effective in reducing cyclosporine-induced GO in rats. Both epithelial and connective tissue showed a decrease in thickness and a significant reduction in TGF-beta2 expression, with a lower number of fibroblasts, reduction in fibrotic areas and decrease in inflammatory infiltrate.

CONCLUSION

The present data suggest that the down-regulation of TGF-beta2 expression may be an important mechanism of action by which roxithromycin inhibits GO.

摘要

背景

牙龈增生(GO)是环孢素(CsA)长期使用的常见副作用,CsA 是一种广泛用于预防移植患者排斥反应的免疫抑制剂。最近的研究报告称,在牙龈增生组织中存在特定细胞因子水平升高,特别是 TGF-β,表明这种生长因子在细胞外基质物质的积累中发挥作用。大环内酯类抗生素阿奇霉素在这种不良反应消退中的有效性也已得到证实。

方法

在这项研究中,我们通过免疫组织化学方法创建了一个实验模型,用于评估罗红霉素在 GO 中的治疗效果和转化生长因子β(TGF-β2)的表达。我们使用了四组共 32 只大鼠。在五周内诱导 GO,并在第六周进行药物治疗,具体分组如下:第 1 组接受生理盐水;第 2 组接受 CsA,并在第六周接受生理盐水治疗;第 3 组接受 CsA,并在第六周接受氨苄青霉素治疗;第 4 组接受 CsA 五周,并在第六周接受罗红霉素治疗。

结果

结果表明,罗红霉素治疗可有效减轻 CsA 诱导的大鼠 GO。上皮组织和结缔组织的厚度均减小,TGF-β2 表达显著减少,成纤维细胞数量减少,纤维化区域减少,炎症浸润减少。

结论

本研究数据表明,下调 TGF-β2 表达可能是罗红霉素抑制 GO 的重要作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5013/2802586/31be5385b638/1472-6831-9-33-7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5013/2802586/31be5385b638/1472-6831-9-33-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5013/2802586/948f5789506c/1472-6831-9-33-1.jpg
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