槲皮素调节HIF-1α/VEGF信号通路对大鼠正畸牙移动过程中牙周组织血管数的影响

doi:10.11958/20240663

天津医药 ›› 2024, Vol. 52 ›› Issue (12): 1251-1255.doi: 10.11958/20240663

槲皮素调节HIF-1α/VEGF信号通路对大鼠正畸牙移动过程中牙周组织血管数的影响

郑雅茹(), 黄毅斌, 苏晓平^△(), 张彦君

第九〇九医院/厦门大学附属东南医院口腔科（邮编363000）

收稿日期:2024-05-28 修回日期:2024-08-15 出版日期:2024-12-15 发布日期:2024-12-17
通讯作者: △E-mail：q15lbl@163.com
作者简介:郑雅茹（1993），女，医师，主要从事乳牙及青少年牙病、牙体缺损树脂美学修复及冠修复方面研究。E-mail：tuez45@163.com

Effects of quercetin on periodontal tissue angiogenesis during orthodontic tooth movement in rats by regulating HIF-1α/VEGF signaling pathway

ZHENG Yaru(), HUANG Yibin, SU Xiaoping^△(), ZHANG Yanjun

Department of Stomatology, The 909th Hospital/Dongnan Hospital of Xiamen University, Zhangzhou 363000, China

Received:2024-05-28 Revised:2024-08-15 Published:2024-12-15 Online:2024-12-17
Contact: △E-mail：q15lbl@163.com

郑雅茹, 黄毅斌, 苏晓平, 张彦君. 槲皮素调节HIF-1α/VEGF信号通路对大鼠正畸牙移动过程中牙周组织血管数的影响[J]. 天津医药, 2024, 52(12): 1251-1255.

ZHENG Yaru, HUANG Yibin, SU Xiaoping, ZHANG Yanjun. Effects of quercetin on periodontal tissue angiogenesis during orthodontic tooth movement in rats by regulating HIF-1α/VEGF signaling pathway[J]. Tianjin Medical Journal, 2024, 52(12): 1251-1255.

摘要/Abstract

摘要：

目的探讨槲皮素（QUE）对大鼠正畸牙移动过程中牙周组织血管数及缺氧诱导因子-1α（HIF-1α)/血管内皮生长因子（VEGF）信号通路的影响。方法正畸牙移动大鼠随机分为模型（Model）组、槲皮素低/高剂量（QUE-L/QUE-H）组、槲皮素高剂量+通路抑制剂YC-1组（QUE-H+YC-1组），每组12只；另取12只为对照组（Control组）。测量各组大鼠第一磨牙移动距离；HE染色观察牙周组织病理变化并统计牙周组织血管数；免疫组化检测牙周组织骨形态发生蛋白（BMP）2、BMP4表达情况；蛋白质印迹检测HIF-1α/VEGF信号通路相关蛋白表达情况。结果 Model组较Control组牙周组织纤维排列分散紊乱，细胞间隙增大，大量炎性细胞浸润及骨吸收陷窝，第一磨牙移动距离增大，牙周组织血管数减少，BMP2、BMP4、HIF-1α、VEGF表达降低（P<0.05）；QUE-L、QUE-H组较Model组牙周组织纤维排列相对紧密，炎性细胞浸润减少，牙槽骨吸收现象减轻，第一磨牙移动距离减小，牙周组织血管数增多，BMP2、BMP4、HIF-1α、VEGF表达升高（P<0.05）；QUE-H+YC-1组较QUE-H组牙周组织纤维排列分散紊乱，细胞间隙明显，炎性细胞浸润加剧，骨吸收陷窝增多，第一磨牙移动距离增大，牙周组织血管数减少，BMP2、BMP4、HIF-1α、VEGF表达降低（P<0.05）。结论槲皮素可促进大鼠正畸牙移动过程中牙周组织血管生成，其作用机制与激活HIF-1α/VEGF信号通路有关。

关键词: 槲皮素, 缺氧诱导因子1, 血管内皮生长因子类, 牙正畸牵引, 牙周组织, 血管重塑

Abstract:

Objective To investigate the impacts of quercetin (QUE) on angiogenesis and hypoxia inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) signaling pathway in periodontal tissue of orthodontic tooth movement in rats. Methods A rat model of orthodontic tooth movement was constructed, and the modeled rats were randomly separated into the model group, the low-dose quercetin treatment (QUE-L) group, the high-dose quercetin treatment (QUE-H) group and the QUE-H+pathway inhibitor YC-1 (QUE-H+YC-1) group, with 12 rats in each group. Another 12 rats were regarded as the control group. The movement distance of the first molar of rats in each group was measured. HE staining was applied to observe the pathological changes of periodontal tissue and count the number of blood vessels generated in periodontal tissue. Immunohistochemistry was applied to detect expression levels of bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 4 (BMP4) in periodontal tissue. Western blot assay was applied to detect the expression of HIF-1α/VEGF signaling pathway related proteins. Results Compared with the control group, the periodontal tissue fibers were scattered and disordered in the model group, with an increased intercellular space, infiltration of a large number of inflammatory cells and bone resorption pits, the movement distance of the first molar increased, the number of periodontal tissue blood vessels decreased, and the expression of BMP2, BMP4, HIF-1α and VEGF decreased (P<0.05). The fibrous arrangement of periodontal tissue was relatively tight in the QUE-L group and the QUE-H group compared to the model group, with reduced infiltration of inflammatory cells and reduced alveolar bone resorption. The movement distance of the first molar decreased, the number of periodontal tissue blood vessels increased, and the expression of BMP2, BMP4, HIF-1α and VEGF increased (P<0.05). Compared with the QUE-H group, the periodontal tissue fibers in the QUE-H+YC-1 group were scattered and disordered, with obvious intercellular gaps, increased infiltration of inflammatory cells and increased bone resorption pits, the movement distance of the first molar increased, the number of blood vessels in periodontal tissue decreased, and the expression of BMP2, BMP4, HIF-1α and VEGF decreased (P<0.05). Conclusion Quercetin can promote angiogenesis in periodontal tissue during orthodontic tooth movement in rats, and its mechanism is related to the activation of the HIF-1α/VEGF signaling pathway.

Key words: quercetin, hypoxia-inducible factor 1, vascular endothelial growth factors, orthodontic extrusion, periodontium, vascular remodeling

中图分类号:

R783.5

图/表 6

表1 各组大鼠第一磨牙移动距离及牙周组织血管数比较 ($\bar{x}\pm s$)

Tab.1 Comparison of travel distance of first molar and number of blood vessels in periodontal tissue of rats between the five groups

组别	第一磨牙移动距离/mm^#	血管数/支^##
Control组	0.00±0.00	3.36±0.22
Model组	0.58±0.06^a	0.75±0.08^a
QUE-L组	0.41±0.04^b	1.81±0.14^b
QUE-H组	0.25±0.03^bc	3.25±0.19^bc
QUE-H+YC-1组	0.49±0.05^d	1.53±0.12^d
F	363.698^＊＊	616.525^＊＊

图1 各组大鼠牙周组织病理学变化（HE，×100） AB：牙槽骨；PL：牙周韧带；D：象牙质。

Fig.1 Periodontal histopathological changes of rats in each group (HE，×100)

图2 Western blot检测HIF-1α、VEGF蛋白表达 A：Control组；B：Model组；C：QUE-L组；D：QUE-H组；E：QUE-H+YC-1组。

Fig.2 Western blot analysis of HIF-1α and VEGF protein expression

表2 各组大鼠牙周组织HIF-1α/VEGF信号通路相关蛋白表达比较（n=6，$\bar{x}\pm s$）

Tab.2 Comparison of HIF-1α/VEGF signaling pathway related protein expression in periodontal tissue of rats between the five groups

组别	HIF-1α	VEGF
Control组	0.92±0.07	1.21±0.11
Model组	0.25±0.03^a	0.33±0.03^a
QUE-L组	0.43±0.04^b	0.62±0.05^b
QUE-H组	0.74±0.06^bc	0.97±0.07^bc
QUE-H+YC-1组	0.35±0.04^d	0.76±0.05^d
F	188.500^＊＊	147.210^＊＊

表3 各组大鼠牙周组织BMP2、BMP4表达比较（n=6，OD值，$\bar{x}\pm s$）

Tab.3 Comparison of BMP2 and BMP4 expression in periodontal tissue of rats between the five groups

组别	BMP2	BMP4
Control组	0.81±0.08	0.87±0.09
Model组	0.31±0.03^a	0.35±0.04^a
QUE-L组	0.52±0.05^b	0.57±0.06^b
QUE-H组	0.77±0.08^bc	0.85±0.09^bc
QUE-H+YC-1组	0.46±0.05^d	0.49±0.05^d
F	72.080^＊＊	65.121^＊＊

图3 各组大鼠BMP2、BMP4表达情况（免疫组化，×100） AB：牙槽骨；PL：牙周韧带；D：象牙质。

Fig.3 Expression of BMP2 and BMP4 in rats in each group ( immunohistochemical, ×100)

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槲皮素调节HIF-1α/VEGF信号通路对大鼠正畸牙移动过程中牙周组织血管数的影响

Effects of quercetin on periodontal tissue angiogenesis during orthodontic tooth movement in rats by regulating HIF-1α/VEGF signaling pathway

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