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环孢素诱导大鼠无牙牙龈过度生长中转化生长因子-β1和血管内皮生长因子基因及蛋白表达上调

Upregulation of transforming growth factor-beta1 and vascular endothelial growth factor gene and protein expression in cyclosporin-induced overgrown edentulous gingiva in rats.

作者信息

Chen Yen-Teen, Tu Hsiao-Pei, Chin Yu-Tang, Shen E-Chin, Chiang Cheng-Yang, Gau Ching-Hwa, Fu Earl

机构信息

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

出版信息

J Periodontol. 2005 Dec;76(12):2267-75. doi: 10.1902/jop.2005.76.12.2267.

DOI:10.1902/jop.2005.76.12.2267
PMID:16332239
Abstract

BACKGROUND

To examine the effects of cyclosporin A (CsA) on the expression of growth factors in induced gingival overgrowth with limited contributing factors arising from local inflammation caused by bacterial plaque, this study of gingival overgrowth was designed on the edentulous ridge of rats.

METHODS

After a 3-week healing period following maxillary molar extractions, 16 five-week-old male Sprague-Dawley rats were assigned to CsA and control groups. Animals in the CsA group were fed 30 mg/kg CsA daily, whereas the control rats received a mineral oil vehicle instead. After 4 weeks, all animals were sacrificed, and the morphology of edentulous ridges was recorded by dental impression. The gingivae on the left-hand side were dissected and stored for mRNA analysis, whereas the gingivae on the right-hand side were fixed in 4% paraformaldehyde for immunohistochemistry (IHC) analysis of transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor beta (PDGF-beta), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF).

RESULTS

The edentulous gingivae were enlarged and the body weights were reduced in the CsA-treated animals compared to controls. The mRNA expressions of TGF-beta1, IGF-1, and VEGF were higher in the gingivae of the CsA group than in the control group. In addition, a greater mRNA expression (7.21-fold) of VEGF was demonstrated in the CsA group than in the control group by real-time polymerase chain reaction (PCR). The percentages of cells staining positive for TGF-beta1 and VEGF were significantly greater in the CsA rats than in the control rats.

CONCLUSIONS

Greater mRNA expression and positive staining for TGF-beta1 and VEGF were observed in the edentulous gingivae of rats that received CsA. Therefore, CsA may upregulate TGF-beta1 and VEGF gene expression and protein secretion in CsA-induced gingival overgrowth.

摘要

背景

为研究环孢素A(CsA)对菌斑所致局部炎症因素有限的诱导性牙龈过度生长中生长因子表达的影响,本研究在大鼠无牙牙槽嵴上设计了牙龈过度生长模型。

方法

拔除上颌磨牙后经过3周愈合期,将16只5周龄雄性Sprague-Dawley大鼠分为CsA组和对照组。CsA组动物每日喂服30 mg/kg CsA,而对照大鼠给予矿物油载体。4周后,处死所有动物,通过牙印模记录无牙牙槽嵴的形态。左侧牙龈解剖后保存用于mRNA分析,而右侧牙龈固定于4%多聚甲醛中用于转化生长因子-β1(TGF-β1)、血小板衍生生长因子β(PDGF-β)、胰岛素样生长因子-1(IGF-1)和血管内皮生长因子(VEGF)的免疫组织化学(IHC)分析。

结果

与对照组相比,CsA处理的动物无牙牙龈增大且体重减轻。CsA组牙龈中TGF-β1、IGF-1和VEGF的mRNA表达高于对照组。此外,通过实时聚合酶链反应(PCR)显示,CsA组VEGF的mRNA表达(7.21倍)高于对照组。CsA大鼠中TGF-β1和VEGF染色阳性细胞的百分比显著高于对照大鼠。

结论

在接受CsA的大鼠无牙牙龈中观察到TGF-β1和VEGF的mRNA表达增加及阳性染色。因此,CsA可能上调CsA诱导的牙龈过度生长中TGF-β1和VEGF基因表达及蛋白分泌。

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