低氧诱导因子2α介导雌激素对大鼠髁突软骨细胞效应的研究  

The effects of estrogen on mandibular condylar chondrocytes via HIF2α

作　　者：牛临生[1] 叶涛 孙东亮 张勉 苗辉 于世宾 NIU Lin-sheng;YE Tao;SUN Dong-liang;ZHANG Mian;MIAO Hui;YU Shi-bin(Department of Stomatology,Shanxi Linfen People＇s Hospital,Linfen 041000,China)

机构地区：[1]山西省临汾市人民医院口腔科,山西临汾041000 [2]军事口腔医学国家重点实验室,陕西省口腔医学重点实验室,第四军医大学口腔医院,陕西西安710032

出　　处：《牙体牙髓牙周病学杂志》2018年第6期321-326,371,共7页Chinese Journal of Conservative Dentistry

基　　金：国家自然科学基金面上项目(81371166);陕西省国家科技合作项目(2014KW21-02)

摘　　要：目的:探讨低氧诱导因子2α(HIF2α)在雌激素刺激下对下颌髁突软骨细胞效应中的作用。方法:取第2代SD大鼠下颌髁突软骨细胞,并将其随机分为4组:对照组、雌激素(1μmol/L)刺激组、雌激素(1μmol/L)刺激+雌激素受体阻断(1μmol/L)组、雌激素(1μmol/L)刺激+HIF2α阻断(5μmol/L)组;分别对各组细胞进行相应刺激并培养12 h后,采用实时定量PCR和Western blot分别检测各组细胞中Aggrecan、Ⅱ型胶原(ColⅡ)、IL-1β、TNF-α、HIF2α及其下游因子MMP13、VEGF、X型胶原(Col X)的mRNA和蛋白表达水平。结果:与对照组相比,雌激素刺激组髁突软骨细胞中Aggrecan、ColⅡ的mRNA表达水平显著降低(P<0.05),IL-1β、TNF-α、HIF2α及其下游因子MMP13、VEGF、Col X的mRNA和蛋白表达水平显著升高(P<0.05);而雌激素受体阻断剂和HIF2α阻断剂则均可显著逆转上述效应(P<0.05)。结论:雌激素可诱发髁突软骨细胞的退行性变,在此过程中雌激素-雌激素受体-HIF2α通路发挥着重要作用。AIM： Toinvestigate the effects of estrogen on mandibular condylar chondrocytes via HIF2α. METHODS： The mandibular condylar chondrocytes from the second passage were divided into control group, estrogen（1 μmol/L）-stimulating group, estrogen-stimulating group, estrogen receptor blocking group and estrogen - stimulating and HIF2α blocking group. The cells were collected after being stimulated for 12 hours. Real-time PCR and western blot were employed to detect the expression of the main cartilage matrix aggrecan（Acan）, collagen type Ⅱ （Col Ⅱ）, proinflammatory cytokines interleukin - 1β （IL - 1β）, tumor nectosis factor - α （TNF - α）, HIF2α, HIF2α downstream cytokines matrix metalloproteinase 13 （MMP13）, vascular endothecial growth factor （VEGF） and collagen type X （Col X）. RESULTS： Stimulation with estrogen at 1 μmol/L significantly decreased the expression of Acan and Col Ⅱ（ P 〈0.05）, but increased the expression of IL-1β, TNF - α, HIF2α, MMP13, VEGF and Col X（ P 〈0.05）. Both specific estrogen receptor blocking agent and specific HIF2α blocking agent reversed the related effect of estrogen（ P 〈0.05）. CONCLUSION： Estrogen can induce degenerative changes of mandibular condylar chondrocytes. The pathway of estrogen - estrogen receptor - HIF2α plays an important role in this process.

关 键 词：雌激素 低氧诱导因子 颞下颌关节 髁突 软骨细胞 

分 类 号：R780.2[医药卫生—口腔医学]