[1]张晓莉,马嘉平*.神经调节蛋白4及其受体ErbB4在牙周炎患者龈沟液中的表达及对牙周炎大鼠牙周组织炎症和牙槽骨丢失的影响[J].徐州医科大学学报,2022,42(05):318-325.[doi:10.3969/j.issn.2096-3882.2022.05.002]
　The ex＜x＞pression of neuregulin 4 (Nrg-4) and its receptor ErbB4 in gingival crevicular fluid of patients with periodontitis and its effect on periodontal tissue inflammation and alveolar bone loss in rats with periodontitis[J].Journal of Xuzhou Medical University,2022,42(05):318-325.[doi:10.3969/j.issn.2096-3882.2022.05.002]
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神经调节蛋白4及其受体ErbB4在牙周炎患者龈沟液中的表达及对牙周炎大鼠牙周组织炎症和牙槽骨丢失的影响()
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《徐州医科大学学报》[ISSN:2096-3882/CN:32-1875/R]

卷:
42
期数:
2022年05期
页码:
318-325
栏目:
出版日期:
2022-05-25

文章信息/Info

Title:
The ex＜x＞pression of neuregulin 4 (Nrg-4) and its receptor ErbB4 in gingival crevicular fluid of patients with periodontitis and its effect on periodontal tissue inflammation and alveolar bone loss in rats with periodontitis
作者:
张晓莉; 马嘉平*
新疆维吾尔自治区人民医院口腔科， 新疆乌鲁木齐830001
关键词:
牙周炎; 龈沟液; ErbB4; 神经调节蛋白4
分类号:
R781.4
DOI:
10.3969/j.issn.2096-3882.2022.05.002
文献标志码:
A
摘要:
目的探讨神经调节蛋白4（Nrg4）及其受体ErbB4在牙周炎患者龈沟液（GCF）中的表达情况及对牙周炎大鼠牙周组织炎症和牙槽骨丢失的影响。方法招募健康志愿者及牙周炎患者80名，分为健康组（H组）、牙周炎组（G组）、Ⅱ期B级牙周炎组（P1组）和Ⅲ期B级牙周炎组（P2组），每组20例。采集GCF，采用ELISA法检测ErbB4和Nrg4的表达量。在体外使用IFNγ+LPS刺激原代骨髓来源巨噬细胞（BMDMs）和树突状细胞（BMDCs），并采用qPCR法测定胞内表皮生长因子受体(EGFR)、ErbB2、ErbB3、ErbB4 mRNA的表达情况。使用Nrg4重组蛋白处理骨髓来源M1巨噬细胞并采用CCK-8法测定其存活能力，采用Annexin V-PI双标记流式细胞术测定其凋亡情况。在体动物实验构建实验性牙周炎动物模型。15只大鼠随机分为假手术组（S组）、模型组（M组）和Nrg4重组蛋白治疗组（T组），每组5只。对3组大鼠上颌骨牙周炎造模部位进行micro-CT成像分析，苏木精-伊红（H-E）染色观察组织病理学变化。结果与H组相比，牙周炎各阶段分组患者GCF中ErbB4的表达量显著升高，Nrg4的表达量显著降低（P<0.05）。在体外使用IFNγ+LPS刺激原代BMDMs引起其内ErbB4 mRNA表达显著上调（P<0.01）。使用Nrg4重组蛋白处理骨髓来源M1巨噬细胞后，其存活能力显著降低，细胞凋亡水平显著升高（P<0.01）。动物实验micro-CT成像分析表明，使用Nrg4重组蛋白治疗牙周炎大鼠模型显示出较好的疗效，与M组相比，T组釉-牙骨质界和牙槽骨嵴（CEJ-ABC）间的距离明显缩小，骨矿物质密度（BMD）和骨体积分数（BV/TV）明显升高（P<0.01）；而与S组相比，T组上述4个参数的测定结果无明显变化（P＞0.05）。结论GCF中ErbB4和Nrg4的表达水平能够作为潜在牙周炎患者炎症水平的标志物,Nrg4重组蛋白治疗牙周炎在在体动物模型水平上显示出了较好的疗效。
Abstract:
ob＜x＞jective: To investigate the ex＜x＞pression of neuregulin 4 (Nrg-4) and its receptor ErbB4 in gingival crevicular fluid (GCF) of patients with periodontitis and their effects on periodontal tissue inflammation and alveolar bone loss in experimental periodontitis rat model. Methods: A total of 20 healthy participants (H group, n=20) and 60 patients with periodontitis were recruited and divided into periodontitis group (G group, n=20), stage II grade B periodontitis group (P1 group, n=20) and stage III grade B periodontitis group (P2 group, n=20). The GCF of all participants was collected, and the ex＜x＞pression levels of ErbB4, Nrg4, IL-6 and IL10 in GCF were detected by using ELISA assay, the ratio of IL-6/IL10 was calculated and Pearson’s correlation analysis was performed. In vivo experimental periodontitis rat model was constructed. A total of 15 rats were randomly divided into sham operation group (S group), model group (M group) and Nrg4 recombinant protein treatment group (T group), 5 rats for each group. Micro-CT imaging analysis, followed by the H&E staining and histopathological analysis were performed to analyze the condition of the above three groups of rats ’ maxillary periodontitis sites. GCF of the three groups of rats was also collected and measured the ratio of IL-6/IL10 to evaluate the inflammation levels. Results: Compared with group H, the ex＜x＞pression of ErbB4 in GCF of patients in the different stages of periodontitis, group G ( p<0.05), group P1 (p<0.01) and group P2 (p<0.01) was significantly increased, and the ex＜x＞pression of ErbB4 in GCF of the group P2 was higher than that of the group G (p<0.05). While, compared with group H, the ex＜x＞pression of Nrg4 in GCF of patients in the different stages of periodontitis, group G (p<0.01), group P1 (p<0.01) and group P2 (p<0.01) was significantly decreased. At the same time, the ex＜x＞pression of ErbB4 in the GCF of periodontitis group G (r2=0.4184, p =0.0021), P1 (r2=0.7314, p<0.0001) and P2 (r2=0.2867, p=0.0150) patients was positively correlated with the ratio of IL-6/IL10 within the group, respectively. The ex＜x＞pression of Nrg4 in the GCF of periodontitis group G (r2=0.4135，p=0.0022), P1 (r2=0.3589，p=0.0052) and P2 (r2=0.3650，p=0.0048) patients was negatively correlated with the ratio of IL-6/IL10 within the group, respectively. In vivo animal model study by using micro-CT imaging analysis showed that the use of Nrg4 recombinant protein to treat periodontitis rat model showed good curative effects. Compared with M group, in the T group, the distance between the cement-enamel junction and the alveolar bone crest (CEJ-ABC) was significantly reduced ( p<0.01), bone mineral density (BMD) (p<0.01) and bone/tissue volum (BV/TV) ( p<0.01) increased significantly; the ratio of IL-6/IL10 decreased significantly (p<0.01), while there is no significant difference of the above 4 parameters between the T group and the S group. Conclusion: The ex＜x＞pression levels of ErbB4 and Nrg4 in GCF can be used as potential markers of inflammatory levels in patients with periodontitis. The Nrg4 recombinant protein has shown a good curative effects in the treatment of periodontitis in vivo.

相似文献/References:

[1]许飞虎,沈想*.牙周序列治疗牙周炎患者正畸过程中的效果分析[J].徐州医科大学学报,2017,37(12):860.
　XU Feihu,SHEN Xiang*.A study on the efficacy of periodontal-sequence treatment duringthe orthodontic treatment of periodontitis patients[J].Journal of Xuzhou Medical University,2017,37(05):860.
[2]沈晓云、王尽尧、徐东菁等.派丽奥软膏辅助龈下超声治疗中重度牙周炎临床疗效观察[J].徐州医科大学学报,2009,29(09):611.
　[J].Journal of Xuzhou Medical University,2009,29(05):611.
[3]许飞虎、沈想.牙周序列治疗牙周炎患者正畸过程中的效果分析[J].徐州医科大学学报,2017,37(12):860.
　[J].Journal of Xuzhou Medical University,2017,37(05):860.

备注/Memo

备注/Memo:
基金项目：新疆维吾尔自治区自然科学基金（2017D01C143）*通信作者,E-mail：hsj1808975@163.com
更新日期/Last Update: 2022-06-07