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褪黑素通过降低大鼠炎症应激和细胞凋亡改善牙周炎引起的肾损伤。

Melatonin improves periodontitis-induced kidney damage by decreasing inflammatory stress and apoptosis in rats.

机构信息

Department of Periodontology, School of Dentistry, Recep Tayyip Erdogan University, Rize, Turkey.

Department of Periodontology, School of Dentistry, Eskişehir Osmangazi University, Eskisehir, Turkey.

出版信息

J Periodontol. 2021 Jun;92(6):22-34. doi: 10.1002/JPER.20-0434. Epub 2020 Nov 30.

Abstract

BACKGROUND

Two main aims of this animal study were to inspect the possible effects of periodontitis on the structure and functions of the kidneys and the therapeutic effectiveness of melatonin.

METHODS

Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Periodontitis was induced by placing 3.0-silk sutures sub-paramarginally around the cervix of right-left mandibular first molars and maintaining the sutures for 5 weeks. Then melatonin (10 mg/kg body weight/day, 14 days), and the vehicle was administered intraperitonally. Mandibular and kidney tissue samples were obtained following the euthanasia. Periodontal bone loss was measured via histological and microcomputed tomographic slices. On right kidney histopathological and immunohistochemical, and on the left kidney biochemical (malonyl-aldehyde [MDA], glutathione, oxidative stress [OSI], tumor necrosis factor [TNF]-α, interleukin [IL]-1β, matrix metalloproteinase [MMP]-8, MMP-9, and cathepsin D levels) evaluations were performed. Renal functional status was analyzed by levels of serum creatinine, urea, cystatin-C, and urea creatinine.

RESULTS

Melatonin significantly restricted ligature-induced periodontal bone loss (P <0 .01) and suppressed the levels of proinflammatory cytokines (TNF-α and IL-1β), oxidative stress (MDA and OSI), and proteases (MMP-8, MMP-9, and CtD) that was significantly higher in the kidneys of the rats with periodontitis (P <0.05). In addition, periodontitis-related histological damages and apoptotic activity were also significantly lower in the Ep-Mel group (P <0.05). However, the markers of renal function of the Ep group were detected slightly impaired in comparison with the control group (P >0.05); and the therapeutic activity of melatonin was limited (P >0.05).

CONCLUSION

Melatonin restricts the periodontitis-induced inflammatory stress, apoptosis, and structural but not functional impairments.

摘要

背景

本动物研究的两个主要目的是检查牙周炎对肾脏结构和功能的可能影响以及褪黑素的治疗效果。

方法

24 只雄性 Sprague-Dawley 大鼠随机分为三组:对照组、实验性牙周炎组(Ep)和 Ep-褪黑素组(Ep-Mel)。通过将 3.0 丝缝线置于右下颚第一磨牙颈缘周围,将缝线维持 5 周来诱导牙周炎。然后,褪黑素(10mg/kg 体重/天,14 天)和载体通过腹腔内给药。安乐死后获得下颌骨和肾脏组织样本。通过组织学和微计算机断层扫描切片测量牙周骨丢失。对右肾组织病理学和免疫组织化学,以及左肾生化(丙二醛 [MDA]、谷胱甘肽、氧化应激 [OSI]、肿瘤坏死因子 [TNF]-α、白细胞介素 [IL]-1β、基质金属蛋白酶 [MMP]-8、MMP-9 和组织蛋白酶 D 水平)进行评估。通过血清肌酐、尿素、胱抑素-C 和尿素肌酐水平分析肾功能状态。

结果

褪黑素显著限制结扎诱导的牙周骨丢失(P<0.01),并抑制牙周炎大鼠肾脏中促炎细胞因子(TNF-α和 IL-1β)、氧化应激(MDA 和 OSI)和蛋白酶(MMP-8、MMP-9 和 CtD)水平升高(P<0.05)。此外,Ep-Mel 组牙周炎相关的组织学损伤和细胞凋亡活性也显著降低(P<0.05)。然而,与对照组相比,Ep 组的肾功能标志物检测到轻微受损(P>0.05);并且褪黑素的治疗活性受到限制(P>0.05)。

结论

褪黑素限制牙周炎引起的炎症应激、细胞凋亡和结构损伤,但不影响功能损伤。

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