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阿托伐他汀加速伴牙周炎的 1 型糖尿病大鼠牙槽骨丢失。

Atorvastatin Accelerates Alveolar Bone Loss in Type 1 Diabetic Rats Submitted to Periodontitis.

机构信息

Post-Graduate Program in Morphological Science, Federal University of Ceara, Fortaleza, Ceara, Brazil.

Post-Graduate Program in Health Science, Federal University of Ceara, Fortaleza, Ceara, Brazil.

出版信息

Braz Dent J. 2024 Oct 28;35:e246100. doi: 10.1590/0103-6440202406100. eCollection 2024.

DOI:10.1590/0103-6440202406100
PMID:39476053
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11520491/
Abstract

Periodontal bone loss is potentiated by diabetes. Despite the beneficial anti-inflammatory and antiresorptive effects of Atorvastatin (ATV) on periodontitis, it has been reported to increase the risk of diabetes, which may modify the course of periodontal disease. Therefore, this study aimed to evaluate the effect of ATV on alveolar bone in rats with periodontitis and diabetes. For this, 72 Wistar rats were divided into groups: Naïve (N) not submitted to any procedure; Experimental periodontitis (EP) group submitted to ligature-induced periodontitis; diabetes mellitus (DM), submitted to EP and receiving single dose of streptozotocin (60 mg/kg, i.p.) after 12 hours of fasting; and ATV DM, submitted to EP and DM and receiving orally 27 mg/kg of ATV, 30 minutes before ligature placement, and continued daily until the 11th day. Animals from EP and DM received saline solution 0.9% as placebo. Glycemic levels measured in all animals and then were euthanized. Maxillae were collected for macroscopic, micro-tomographic, and microscopic analyses. DM caused intense bone loss (60%), characterized by a reduction in trabecular thickness and bone volume. DM reduced osteoblasts, increasing osteoclast counts, and induced an inflammatory infiltrate in the periodontium. ATV was found ineffective in protecting bone in diabetic rats, exacerbating bone loss by 21%. Additionally, ATV significantly increased blood glucose levels. In summary, ATV did not prevent alveolar bone loss or modulate inflammation in DM animals undergoing EP. ATV also increased blood glucose levels in these animals. Therefore, the systemic use of ATV in uncontrolled diabetic conditions should be carefully evaluated.

摘要

牙周骨丢失会被糖尿病加重。尽管阿托伐他汀(ATV)对牙周炎具有有益的抗炎和抗吸收作用,但它已被报道会增加患糖尿病的风险,这可能会改变牙周病的病程。因此,本研究旨在评估 ATV 对患有牙周炎和糖尿病的大鼠牙槽骨的影响。为此,将 72 只 Wistar 大鼠分为以下几组:未处理的(N),未进行任何处理;实验性牙周炎(EP)组,结扎诱导牙周炎;糖尿病(DM)组,结扎诱导牙周炎并在禁食 12 小时后接受单次链脲佐菌素(60mg/kg,腹腔注射);和 ATV DM 组,结扎诱导牙周炎和 DM 并在结扎放置前 30 分钟接受 27mg/kg 的 ATV 口服治疗,并持续每日治疗直至第 11 天。EP 和 DM 组的动物接受 0.9%生理盐水作为安慰剂。所有动物的血糖水平均进行了测量,然后进行安乐死。收集上颌骨进行宏观、微计算机断层扫描和显微镜分析。DM 导致严重的骨丢失(60%),表现为骨小梁厚度和骨量减少。DM 减少了成骨细胞,增加了破骨细胞计数,并在牙周组织中诱导了炎症浸润。在糖尿病大鼠中,ATV 对保护骨没有作用,反而使骨丢失增加了 21%。此外,ATV 还显著增加了血糖水平。综上所述,在接受 EP 的 DM 动物中,ATV 既不能预防牙槽骨丢失,也不能调节炎症。ATV 还会增加这些动物的血糖水平。因此,在未控制的糖尿病情况下,应谨慎评估全身使用 ATV 的安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5e/11520491/1d4d5d885bdf/1806-4760-bdj-35-e24-6100-gf3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5e/11520491/90c701d7d157/1806-4760-bdj-35-e24-6100-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5e/11520491/b82c5c0029a4/1806-4760-bdj-35-e24-6100-gf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5e/11520491/1d4d5d885bdf/1806-4760-bdj-35-e24-6100-gf3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5e/11520491/90c701d7d157/1806-4760-bdj-35-e24-6100-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5e/11520491/b82c5c0029a4/1806-4760-bdj-35-e24-6100-gf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b5e/11520491/1d4d5d885bdf/1806-4760-bdj-35-e24-6100-gf3.jpg

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本文引用的文献

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Current Concepts in the Management of Periodontitis.牙周炎治疗的现状。
Int Dent J. 2021 Dec;71(6):462-476. doi: 10.1111/idj.12630. Epub 2021 Feb 19.
2
Hyperglycemia impairs osteoblast cell migration and chemotaxis due to a decrease in mitochondrial biogenesis.高血糖会由于线粒体生物发生减少而损害成骨细胞的迁移和趋化性。
Mol Cell Biochem. 2020 Jun;469(1-2):109-118. doi: 10.1007/s11010-020-03732-8. Epub 2020 Apr 18.
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The Interplay Between Bone and Glucose Metabolism.骨与糖代谢的相互作用。
Front Endocrinol (Lausanne). 2020 Mar 24;11:122. doi: 10.3389/fendo.2020.00122. eCollection 2020.
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Loss of Dkk-1 in Osteocytes Mitigates Alveolar Bone Loss in Mice With Periodontitis.成骨细胞中 Dkk-1 的缺失可减轻牙周炎小鼠的牙槽骨丢失。
Front Immunol. 2019 Dec 10;10:2924. doi: 10.3389/fimmu.2019.02924. eCollection 2019.
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The impact of diabetes on periodontal diseases.糖尿病对牙周病的影响。
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Efficacy of locally-delivered statins adjunct to non-surgical periodontal therapy for chronic periodontitis: a Bayesian network analysis.局部给予他汀类药物辅助非手术牙周治疗慢性牙周炎的疗效:贝叶斯网络分析。
BMC Oral Health. 2019 Jun 13;19(1):105. doi: 10.1186/s12903-019-0789-2.
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Simvastatin attenuates tibial bone loss in rats with type 1 diabetes and periodontitis.辛伐他汀可减轻 1 型糖尿病伴牙周炎大鼠胫骨骨量丢失。
J Transl Med. 2018 Nov 9;16(1):306. doi: 10.1186/s12967-018-1681-6.
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Periodontal diseases.牙周病。
Nat Rev Dis Primers. 2017 Jun 22;3:17038. doi: 10.1038/nrdp.2017.38.
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Efficacy of Subgingivally Delivered 1.2% Atorvastatin in the Treatment of Chronic Periodontitis in Patients With Type 2 Diabetes Mellitus: A Randomized Controlled Clinical Trial.龈下给予1.2%阿托伐他汀治疗2型糖尿病患者慢性牙周炎的疗效:一项随机对照临床试验
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