山姜素抑制类风湿关节炎大鼠关节滑膜血管生成的机制研究OA
Mechanistic Study on Alpinetin-Mediated Suppression of Synovial Angiogenesis in Rheumatoid Arthritis Rats
目的:探究山姜素调节缺氧诱导因子-1α/血管内皮生长因子(HIF-1α/VEGF)通路对类风湿关节炎(RA)大鼠血管生成的影响.方法:采用Ⅱ型胶原蛋白诱导法构建类风湿关节炎大鼠模型,将大鼠分为对照组、关节炎组、山姜素组、泼尼松龙组和山姜素+氯化钴组,检测各组大鼠关节炎指数、关节肿胀程度及体重以分析临床特征;ELISA测定各组大鼠血清中IL-17、IL-6和IL-1β含量;HE染色试剂和番红O固绿进行踝关节病理特征分析;免疫组织化学(IHC)和免疫组织荧光(IHF)检测血管生成数量;Western Blot法检测滑膜组织中HIF-1α、VEGF、VEGFR、CD31蛋白水平.结果:与对照组比较,关节炎组大鼠关节炎指数、关节肿胀程度、IL-17含量、IL-6含量、IL-1β含量、踝关节HE评分、番红O评分、CD31阳性表达量、新生血管数量、成熟血管数量、总血管数量、HIF-1α蛋白水平、VEGF蛋白水平、VEGFR蛋白水平、CD31蛋白水平均上调,体重下降,差异有统计学意义(P<0.05);与关节炎组比较,山姜素组和泼尼松龙组大鼠关节炎指数、关节肿胀程度、IL-17含量、IL-6含量、IL-1β含量、踝关节HE评分、番红O评分、CD31阳性表达量、新生血管数量、HIF-1α蛋白水平、VEGF蛋白水平、VEGFR蛋白水平、CD31蛋白水平均下调,体重上升,差异有统计学意义(P<0.05);与山姜素组比较,山姜素+氯化钴组大鼠关节炎指数、关节肿胀程度、IL-17含量、IL-6含量、IL-1β含量、踝关节HE评分、番红O评分、CD31阳性表达量、新生血管数量、HIF-1α蛋白水平、VEGF蛋白水平、VEGFR蛋白水平、CD31蛋白水平均上调,体重下降,差异有统计学意义(P<0.05),泼尼松龙组大鼠上述指标变化差异无统计学意义(P>0.05).结论:山姜素抑制HIF-1α/VEGF通路,缓解类风湿关节炎大鼠血管生成.
Objective:To investigate the effect of alpinetin on angiogenesis in rheumatoid arthritis(RA)rats by adjusting hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)pathway.Methods:The RA rat model was constructed using type II collagen induction method.The rats were separated into control group,arthritis model group,alpinetin treatment group,prednisolone treatment group,and alpinetin+cobalt chloride group.The arthritis index,joint swelling,and body weight of rats were measured to analyze clinical features.ELISA was used to measure the serum IL-17,IL-6,and IL-1β of rats in each group.HE staining reagent and safranin O-green were used to discuss the pathologi-cal features of ankle joints.Immunohistochemistry(IHC)and immunohistochemistry fluorescence(IHF)were used to detect the quantity of angiogenesis.Western Blot was used to detect the HIF-1α,VEGF,VEGFR,and CD31 proteins in synovial tissue.Results:Compared with the control group,the arthritis model group showed upregulation of arthritis index,joint swelling,IL-17 content,IL-6 content,IL-1β content,ankle HE score,safranin O score,CD31 positivity,number of new blood vessels,number of mature blood vessels,total blood vessels,HIF-1α protein,VEGF protein,VEGFR pro-tein,and CD31 protein,while downregulation of weight(P<0.05).Compared with the arthritis model group,the alpinetin treatment group and prednisolone treatment group showed downregulation of arthritis index,joint swelling,IL-17 content,IL-6 content,IL-1β content,ankle HE score,safra-nin O score,CD31 positivity,number of new blood vessels,HIF-1α protein,VEGF protein,VEGFR protein,and CD31 protein,while upregulation of weight(P<0.05).Compared with the alpinetin treatment group,the alpinetin+cobalt chloride group showed upregulation of arthritis index,joint swelling,IL-17 content,IL-6 content,IL-1β content,ankle HE score,safranin O score,CD31 positivity,number of new blood vessels,HIF-1α protein,VEGF protein,VEGFR protein,and CD31 protein,while downregulation of weight(P<0.05).The above indicators in the prednisolone treatment group were not prominently different(P>0.05).Conclusion:Alpinetin inhibits the HIF-1α/VEGF pathway and alleviates angiogenesis in RA rats.
王贺;刘佳;刘畅
唐山市中心医院(河北 唐山,063000)唐山市中心医院(河北 唐山,063000)唐山市中心医院(河北 唐山,063000)
医药卫生
山姜素缺氧诱导因子-1α/血管内皮生长因子通路类风湿关节炎血管生成
alpinetinhypoxia-inducible factor-1α/vascular endothelial growth factor pathwayrheumatoid arthritisangiogenesis
《中国中医骨伤科杂志》 2026 (2)
28-34,7
河北省医学科学研究重点课题计划项目(20231838)
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