PT2399通过抑制HIF-2α对小鼠关节软骨的保护作用  

PT2399 Protects the Cartilage Degeneration of the Joints by Inhibiting HIF-2α in Mice

作　　者：周永 冯罡宁 丁冬 胡学宇 燕江波 唐志群 金群华[2] ZHOU Yong;FENG Gangning;DING Dong;HU Xueyu;YAN Jiangbo;TANG Zhiqun;JIN Qunhua(School of Clinical Medical Sciences,Ningxia Medical University,Yinchuan 750004,China;General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学临床医学院,银川750004 [2]宁夏医科大学总医院,银川750004

出　　处：《宁夏医科大学学报》2022年第6期555-560,共6页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金项目(2021AAC03396;2020AAC03390;2020AAC03392)。

摘　　要：目的探讨HIF-2α以及相关因子在骨关节炎发展中的保护作用。方法取30只8周龄雄性C57BL/6小鼠,随机分为对照组(不进行处理)、模型组(行内侧半月板失稳术造模)、治疗组(造模后用PT2399治疗),各10只,使用番红O固绿和HE染色分析小鼠软骨的损伤情况;使用国际骨关节炎研究学会(OARSI)评分评估小鼠膝关节软骨样品的退化程度;使用免疫组织化学(IHC)和免疫荧光(IF)实验检测软骨组织中HIF-2α、MMP13、β-catenin和Ⅱ型胶原的表达情况。使用qRT-PCR检测软骨组织中HIF-2α和β-catenin的mRNA表达量。结果在HE和番红O固绿染色实验中,透明软骨厚度:对照组>治疗组>模型组,OARSI评分:对照组<治疗组<模型组(P均<0.01);IHC和IF结果可见,Ⅱ型胶原表达量:模型组<治疗组<对照组,HIF-2α、β-catenin和MMP13蛋白的表达量:对照组<治疗组<模型组(P均<0.01);实时荧光定量PCR实验结果可见,HIF-2α和β-catenin的mRNA表达量:对照组<治疗组<模型组(P均<0.01)。结论PT2399可以通过抑制HIF-2α表达从而发挥对软骨保护作用。Objective To explore the protective effect of HIF-2αand related factors in the development of osteoarthritis.Methods Thirty 8-week-old male C57BL/6 mice were randomly divided into a control group(no treatment),a model group(with medial meniscus instability),and a treatment group(treated with PT2399 after modeling).Each of ten mice was stained with Safranin O Fast Green and HE to analyze the damage of mouse cartilage.OARSI was used to evaluate the degree of degeneration in mouse knee cartilage samples.Immunohistochemistry(IHC)and immunofluorescence(IF)experiments were used to detect expression of HIF-2α,MMP13,β-catenin and type Ⅱ collagen in cartilage tissue.The mRNA expressions of HIF-2αandβ-catenin in cartilage tissue were detected by qRT-PCR.Results In the HE and Safranin O Fast Green staining experiments,the thickness of hyaline cartilage showed control group>treatment group>model group,and OARSI score showed control group<treatment group<model group(P all<0.01).IHC and IF results showed that type Ⅱ collagen expression:model group<treatment group<control group,expression of HIF-2α,β-catenin and MMP13 proteins:control group<treatment group<model group(P all<0.01).Real-time quantitative PCR test results showed that the mRNA expression levels of HIF-2αandβ-catenin:control group<treatment group<model group(P all<0.01).Conclusion PT2399 can exert a protective effect on cartilage by inhibiting the expression of HIF-2α.

关 键 词：骨关节炎 软骨 缺氧诱导因子2α Β-CATENIN WNT信号通路 

分 类 号：R336[医药卫生—人体生理学]