SIRT1在M/CMCS治疗慢性牙周炎牙槽骨丢失的机制研究

doi:10.3969/j.issn.1006-6233.2023.10.004

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摘要 目的:探究SIRT1在甲硝唑羧甲基壳聚糖凝胶治疗慢性牙周炎大鼠牙槽骨丢失及TLR4/NF-κB信号的中的作用机制。方法:将50只大鼠随机分为NC组、Model组、M/CMCS组、MNZ组、M/CMCS+EX527组,每组10只。检测大鼠牙周组织临床指标(BI、PD);ELISA检测血清中IL-6、IL-1β、TNF-α水平;micro-CT检测骨矿物质密度(BMD,骨体积/总体积(BV/TV),釉-牙骨质界(CEJ)至牙槽骨嵴(ABC)间的距离;HE染色检测各组大鼠牙周组织病理学变化;蛋白质印迹法检测牙周组织中TLR4、NF-κB p65、SIRT1蛋白表达。结果:和NC组相比,Model组大鼠PD(2.28±0.21)、BI(3.76±0.30)、血清中TNF-α(234.05±11.62)、IL-1β(203.62±15.31)、IL-6(181.35±11.27)水平、CEJ-ABC(615.34±51.45)及牙周组织中TLR4(0.53±0.06)和NF-κB p65(0.75±0.08)蛋白表达均明显升高,BMD(0.32±0.03)、BV/TV值(31.02±1.57)及牙周组织中SIRT1蛋白(0.21±0.03)表达降低(P<0.0001);和Model组相比,M/CMCS组和MNZ组PD(0.81±0.08)、(1.23±0.13)、BI(1.24±0.12)、(1.89±0.15)、血清中TNF-α(75.81±7.54)、(115.36±8.23)、IL-1β(93.21±8.15)、(122.48±9.02)、IL-6(76.81±6.32)、(105.04±7.11)水平、CEJ-ABC(276.17±27.28)、(361.35±30.94)及牙周组织中TLR4(0.21±0.03)、(0.28±0.03)和NF-κB p65(0.36±0.04)、(0.42±0.05)蛋白表达均明显降低,BMD(0.54±0.05)、(0.42±0.05)和BV/TV(45.91±2.06)、(39.87±2.41)值及牙周组织中SIRT1(0.72±0.08)、(0.25±0.06)蛋白表达增加,且M/CMCS组变化最显著(P<0.0001);和M/CMCS组相比,M/CMCS+EX527组大鼠BI(3.18±0.27)、PD(2.10±0.18)、血清中TNF-α(208.54±10.81)、IL-1β(191.25±12.37)、IL-6(173.26±10.04)水平、CEJ-ABC(601.82±50.29)及牙周组织中TLR4(0.50±0.05)和NF-κB p65蛋白(0.71±0.07)表达均明显升高,BMD(0.35±0.04)、BV/TV(35.62±1.64)及牙周组织中SIRT1蛋白(0.25±0.03)表达值降低(P<0.0001)。结论:甲硝唑羧甲基壳聚糖凝胶可促进慢性牙周炎大鼠牙槽骨重建,修复牙周组织,抑制TLR4/NF-κB信号通路,其机制和激活SIRT1表达有关。

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	尹皓云
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关键词 ：甲硝唑羧甲基壳聚糖凝胶, 慢性牙周炎, 牙槽骨丢失TLR4/NF-κB信号通路, SIRT1

Abstract：Objective: To investigate the mechanism of SIRT1 in the treatment of alveolar bone loss and TLR4/NF-κB signaling in rats with chronic periodontitis by metronidazole carboxymethyl chitosan gel. Methods: Fifty rats were randomly divided into five groups: NC group, Model group, M/CMCS group, MNZ group and M/CMCS+EX527 group, with 10 rats in each group. Clinical indicators of periodontal tissues (BI, PD) were measured in the rats. ELISA was used to measure the levels of IL-6, IL-1βand TNF-α in serum. Micro-CT was used to measure the bone mineral density (BMD), bone volume/total volume (BV/TV), and the distance between the cemento-enamel junction (CEJ) and alveolar bone crest (ABC). HE staining was performed to examine the histopathological changes in periodontal tissues. Protein immunoblotting was used to detect the expression of TLR4, NF-κB p65, and SIRT1 proteins in periodontal tissues. Results: Compared to the NC group, the rats in the model group showed significant increases in PD (2.28±0.21), BI (3.76±0.30), levels of TNF-α (234.05±11.62), IL-1β (203.62±15.31), and IL-6 (181.35±11.27) in serum, CEJ-ABC distance (615.34±51.45), and protein expression of TLR4 (0.53±0.06) and NF-κB p65 (0.75±0.08) in periodontal tissues, as well as decreases in BMD (0.32±0.03), BV/TV (31.02±1.57), and protein expression of SIRT1 (0.21±0.03) in periodontal tissues (P<0.0001). Compared to the model group, the M/CMCS group and MNZ group showed significant decreases in PD (0.81±0.08), (1.23±0.13), BI (1.24±0.12), (1.89±0.15), levels of TNF-α (75.81±7.54), (115.36±8.23), IL-1β (93.21±8.15), (122.48±9.02), and IL-6 (76.81±6.32), (105.04±7.11) in serum, CEJ-ABC distance (276.17±27.28), (361.35±30.94), and protein expression of TLR4 (0.21±0.03), (0.28±0.03) and NF-κB p65 (0.36±0.04), (0.42±0.05) in periodontal tissues, as well as increases in BMD (0.54±0.05), (0.42±0.05), BV/TV (45.91±2.06), (39.87±2.41), and protein expression of SIRT1 (0.72±0.08), (0.25±0.06) in periodontal tissues, with the M/CMCS group showing the most significant changes (P<0.0001). Compared to the M/CMCS group, the rats in the M/CMCS+EX527 group showed significant increases in BI (3.18±0.27), PD (2.10±0.18), levels of TNF-α (208.54±10.81), IL-1β (191.25±12.37), and IL-6 (173.26±10.04) in serum, CEJ-ABC distance (601.82±50.29), and protein expression of TLR4 (0.50±0.05) and NF-κB p65 (0.71±0.07) in periodontal tissues, as well as decreases in BMD (0.35±0.04), BV/TV (35.62±1.64), and protein expression of SIRT1 (0.25±0.03) in periodontal tissues (P<0.0001). Conclusion: Metronidazole carboxymethyl chitosan gel can promote alveolar bone reconstruction and repair periodontal tissues in rats with chronic periodontitis and inhibit TLR4/NF-κB signaling pathway by a mechanism related to the activation of SIRT1 expression.

Key words： Metronidazole carboxymethyl chitosan gel/M/CMCS Chronic periodontitis Alveolar bone loss TLR4/NF-κB signaling pathway SIRT1

基金资助:四川青年创新科研课题计划,(编号:Q20003)

引用本文:

尹皓云, 曹阳, 张婷, 范丽苑. SIRT1在M/CMCS治疗慢性牙周炎牙槽骨丢失的机制研究[J]. 河北医学, 2023, 29(10): 1606-1612.
YIN Haoyun, CAO Yang, ZHANG Ting, et al. Mechanisms of SIRT1 in M/CMCS for Alveolar Bone Loss and TLR4/NF-κB Signaling in Chronic Periodontitis. HeBei Med, 2023, 29(10): 1606-1612.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.10.004 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I10/1606

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