RANKL/OPG在高原低氧条件下兔牙周炎发病机制中的作用

Role of RANKL/OPG in periodontitis rabbits exposed to hypoxia in high altitude

目的研究模拟高原低氧条件下兔牙周炎的病理改变以及与破骨细胞相关的核因子κB受体活化子配体(receptor activator of nuclear factor-κB ligand,RANKL)、骨保护素(osteoprotegerin,OPG)的相关性。方法 40只家兔完全随机分成4组:平原实验组、平原对照组、高原实验组、高原对照组,每组各10只。通过钢丝结扎切牙方法建立家兔牙周炎模型,动物于分组饲养8周后处死,制作牙周组织石蜡切片,HE染色观察牙周组织病理变化、破骨细胞的表达,荧光免疫组化检测牙周组织中RANKL、OPG的表达。免疫荧光组化采用激光扫描共聚焦显微镜对实验组与对照组RANKL、OPG进行半定量分析,并比较其差异。结果高原实验组与平原实验组、高原对照组和平原对照组RANKL灰度值分别为(1.799±0.036)、(1.519±0.061)、(1.242±0.078)、(0.963±0.098),差异有统计学意义(P<0.05),与高原对照组比较,高原实验组OPG表达降低无统计学意义。高原实验组RANKL与牙周指数呈正相关(P<0.01)。结论高原低氧条件下可能通过改变破骨细胞的RANKL/OPG调节途径促进牙周炎的发生、发展。

Objective To observe the pathological changes of rabbit periodontitis model exposed to hypoxia in high altitude and investigate the roles of receptor activator of nuclear factor-κB ligand（RANKL） and osteoprotegerin（OPG） in the process.Methods Forty rabbits were randomly divided into following groups,plain experimental group,plain control group,plateau experimental group,and plateau control group（n=10）.The periodontitis models were established by ligating the two central incisors of mandible and being raised by high-glucose diets.The animals of control and experimental groups were exposed to normoxia or hypoxia conditions respectively.All rabbits were sacrificed after 8 weeks.Pathological changes of periodontitis and morphology of osteoclasts were observed by HE staining,and the expression of RANKL and OPG in periodontitis tissue were tested by fluorescent light immunofluorescence assay.RANKL,OPG were semi-quantitatively analyzed by laser scanning and confocal microscopy.Results The RANKL gray values were 1.799±0.036,1.519±0.061 respectively in the plateau group and plain group,significantly higher than in the plateau control group and plain control group（1.242±0.078 and 0.963±0.098,P0.05）.Compared to the plateau control group,OPG was lower in the plateau experimental group,but no significant difference was found between them（P0.05）.RANKL expression was positively correlated with periodontal indexes,including plaque index（PLI）,bleeding index（BI）,and attachment loss（AL） in the plateau experimental group（P0.01）.Conclusion Hypoxia environment improves the incidence and progress of periodontitis by changing the RANKL/OPG system in osteoclasts.