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一个改善牙周病损伤的新靶点:与大鼠特异性大麻素受体相比,瞬时受体电位香草素型-1的作用。

A new target to ameliorate the damage of periodontal disease: The role of transient receptor potential vanilloid type-1 in contrast to that of specific cannabinoid receptors in rats.

机构信息

Department of Physiology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.

National Council of Scientific and Technical Research (CONICET), Buenos Aires, Argentina.

出版信息

J Periodontol. 2019 Nov;90(11):1325-1335. doi: 10.1002/JPER.18-0766. Epub 2019 Jun 6.

DOI:10.1002/JPER.18-0766
PMID:31077362
Abstract

BACKGROUND

Transient receptor potential vanilloid type-1 (TRPV1) is expressed in oral tissues cells and its activity can be regulated by inflammation products and anandamide. The aim of the present study was to evaluate the effects of blocking TRPV1 or specific cannabinoid receptors 1 (CB1r) and 2 (CB2r) on periodontal status of rats subjected to experimental periodontitis (EP).

METHODS

Male rats were distributed in groups 1) control, 2) lipopolysaccharide-induced EP (LPS), and 3) LPS plus capsazepine (Capz, TRPV1 antagonist) application (LPS+Capz). EP was induced by injections of LPS (1 mg/mL) around first molars and treatment was performed with Capz (2 µg/mL) applied locally during 6 weeks. Additional experiment was performed by applying CB1r and CB2r antagonists (AM251 and AM630) to rats with EP.

RESULTS

Capz prevented alveolar bone loss (ABL) on the external crests and in the interradicular bone of the first molars (periodontal space height: LPS, 270.7 ± 33.5µm versus LPS+Capz, 216.4 ± 19.9 µm; P <0.01). Inflammatory mediators, like tumor necrosis factor-alpha and prostaglandin E , increased by LPS-induced EP, were diminished in gingival tissue of rats treated with Capz. In contrast, application of AM251 and AM630 exacerbated ABL and gingival inflammatory mediators, increased by LPS, altering also biomechanical properties.

CONCLUSIONS

TRPV1 blockade attenuates periodontal impairment in EP rats, since it reduces local inflammation, unlike CB1r and CB2r blockade. This work lays the foundation for developing therapeutics in humans based on the pharmacological manipulation of these receptors to treat periodontal disease.

摘要

背景

瞬时受体电位香草酸型 1(TRPV1)在口腔组织细胞中表达,其活性可受炎症产物和大麻素调节。本研究旨在评估阻断 TRPV1 或特定大麻素受体 1(CB1r)和 2(CB2r)对实验性牙周炎(EP)大鼠牙周状况的影响。

方法

雄性大鼠分为 3 组:1)对照组,2)脂多糖诱导的 EP(LPS)组,和 3)LPS 加辣椒素(Capz,TRPV1 拮抗剂)处理组(LPS+Capz)。通过在第一磨牙周围注射 LPS(1mg/mL)诱导 EP,并用 Capz(2μg/mL)局部处理 6 周。通过向 EP 大鼠应用 CB1r 和 CB2r 拮抗剂(AM251 和 AM630)进行了额外的实验。

结果

Capz 可预防第一磨牙外嵴和根间骨的牙槽骨丧失(ABL)(牙周间隙高度:LPS 组为 270.7±33.5μm,LPS+Capz 组为 216.4±19.9μm;P<0.01)。LPS 诱导的 EP 导致炎性介质(如肿瘤坏死因子-α和前列腺素 E)增加,而用 Capz 处理的大鼠牙龈组织中这些介质减少。相反,AM251 和 AM630 的应用加剧了 LPS 引起的 ABL 和牙龈炎症介质增加,同时改变了生物力学特性。

结论

TRPV1 阻断减轻了 EP 大鼠的牙周损伤,因为它减轻了局部炎症,与 CB1r 和 CB2r 阻断不同。这项工作为基于这些受体的药理学操作来治疗牙周病开发人类治疗方法奠定了基础。

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