牙种植体周围黏膜炎龈沟液中低氧诱导因子-1α、基质金属蛋白酶-2的水平及意义

Detection levels and significance of HIF-1α and MMP-2 in gingival crevicular fluid of peri-implant mucositis

目的检测牙种植体周围黏膜炎病人龈沟液中低氧诱导因子-1α(HIF-1α)、基质金属蛋白酶-2(MMP-2)表达水平,探讨两者在种植体周围黏膜炎发病程度中的关系及作用。方法选取2017年9月至2019年6月湖南中医药高等专科学校附属第一医院收治的种植体周围黏膜炎病人46例作为研究对象,选取种植体周围炎病人48例、种植体周围牙龈健康者50例作为对照。分别采集种植体周围黏膜炎病人和健康体检者龈沟液,利用酶联免疫吸附法(ELISA)检测龈沟液中HIF-1α、MMP-2、白细胞介素-1β(IL-1β)、核因子-κB(NF-κB)、超氧化物歧化酶(SOD)、丙二醛(MDA)的表达水平,观察记录种植体周菌斑指数(PLI)、牙龈指数(GI)、龈沟出血指数(SBI)、探诊深度(PD)值;采用Pearson法分析种植体周围黏膜炎病人龈沟液中HIF-1α、MMP-2水平与IL-1β、NF-κB、SOD、MDA水平、PLI、GI、SBI、PD值的相关性。采用受试者工作特征(ROC)曲线分析HIF-1α、MMP-2对种植体周围黏膜炎的预测价值。结果随着种植体周围黏膜炎的发生及发展,病人种植体周围龈沟液中HIF-1α、MMP-2、NF-κB、MDA、PLI、GI、SBI、PD值明显升高,周围炎组、黏膜炎组、健康组HIF-1α分别为(587.32±123.11)μg/L、(503.24±116.54)μg/L、(289.67±97.68)μg/L(P<0.05),SOD水平分别为(185.29±15.82)μg/L、(218.82±18.63)μg/L、(234.25±29.88)μg/L(P<0.05),IL-1β水平分别为(22.03±3.34)μg/L、(21.18±3.29)μg/L、(19.51±2.72)μg/L(P<0.05);种植体周围黏膜炎病人龈沟液中HIF-1α、MMP-2水平与IL-1β、NF-κB水平、PLI、GI、SBI、PD值,MMP-2水平与MDA水平均明显正相关(P<0.05),HIF-1α、MMP-2水平与SOD水平均明显负相关(P<0.05);ROC曲线分析结果显示,龈沟液HIF-1α、MMP-2水平检测的ROC曲线下面积为0.799(95%CI:0.708-0.890),敏感度为68.8%,特异性为87.0%。结论龈沟液中HIF-1α、MMP-2表达水平可能与牙种植体周围黏膜炎的发生发展有关,且与炎性因子、氧化应激相关物质、种植体周指标关系密切,可能对种植体周围黏膜炎的发展具有一定的预测价值。

Objective To detect the expressions of hypoxia inducible factor-1α(HIF-1α)and matrix metalloproteinase-2(MMP-2)in gingival crevicular fluid of patients with peri-implant mucositis,and to explore their relationship and role in the pathogenesis of periimplant mucositis.Methods Forty-six patients with peri-implant mucositis admitted to The First Affiliated Hospital of Hunan College of Traditional Chinese Medicine from September 2017 to June 2019 were selected as the research objects,48 patients with peri-implantitis and 50 persons with healthy peri-implant gingiva were selected as the control group.Gingival crevicular fluid was collected from patients with peri-implant mucositis and healthy controls respectively.The expression levels of HIF-1α,MMP-2,interleukin-1β(IL-1β),Nuclear factor kappa B(NF-κB),superoxide dismutase(SOD)and malondialdehyde(MDA)in gingival crevicular fluid were detected by enzyme-linked immunosorbent assay(ELISA).The values of plaque index(PLI),gingival index(GI),sulcus bleeding index(SBI)and probing depth(PD)around implants were observed and recorded.The Pearson correlation method was used to analyze the correlations between HIF-1α,MMP-2 levels in gingival crevicular fluid and IL-1β,NF-κB,SOD,MDA levels,PLI,GI,SBI and PD values in patients with peri-implant mucositis.Receiver operating characteristic(ROC)curve was used to analyze the value of HIF-1αand MMP-2 in predicting the development of peri-implant mucositis.Results With the occurrence and development of peri-implant mucositis,the values of HIF-1α,MMP-2,NF-κB,MDA,PLI,GI,SBI and PD increased significantly[HIF-1α:peri-implantitis group(587.32±123.11)μg/L,peri-implant mucositis group(503.24±116.54)μg/L,healthy control group(289.67±97.68)^([29]);P<0.05],the levels of SOD decreased significantly[peri-implantitis group(185.29±15.82)p g/L,peri-implant mucositis group(218.82±18.63)p g/L,healthy control group(234.25±29.88)μg/L;P<0.05],and the levels of IL-1βincreased[peri-implantitis group(22.03±3.34)μg/L,peri-implant mucositis group(21.18±3.29)μg/L,healthy control group(19.51±2.72)μg/L;P<0.05].The levels of HIF-1αand MMP-2 in gingival crevicular fluid of patients with peri-implant mucositis were positively correlated with the levels of IL-1β,NF-κB,PLI,GI,SBI and PD,while negatively correlated with the level of SOD(P<0.05),and MMP-2 level was positively correlated with MDA level(P<0.05).ROC curve analysis results showed that the area under ROC curve was 0.799(95%CI:0.708-0.890),the sensitivity was 68.8%,and the specificity was 87.0%.Conclusions The expressions of HIF-1αand MMP-2 in gingival crevicular fluid are likely to be related to the occurrence and development of peri-implant mucositis,and are closely related to inflammatory factors,oxidative stress-related substances and periimplant indicators,which may have certain predictive values for the development of peri-implant mucositis.