清络饮通过调控HIF-1α/VEGF通路抑制佐剂诱导关节炎大鼠的滑膜血管新生  

Qingluo Yin inhibits synovial angiogenesis induced by adjuvant in arthritis rats by regulating HIF-1α/VEGF pathway

作　　者：王培培[1] 潘林坤 杨魁 冯丹丹 WANG Peipei;PAN Linkun;YANG Kui;FENG Dandan(Yijishan Hospital of Wannan Medical College,Wuhu 241001,Anhui,China;Department of Pharmacy,Wannan Medical College,Wuhu 241002,Anhui,China)

机构地区：[1]皖南医学院弋矶山医院,安徽芜湖241001 [2]皖南医学院药学院,安徽芜湖241002

出　　处：《中国临床药理学与治疗学》2025年第3期366-373,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：皖南医学院校中青年科研项目(WK2022F11);安徽省高等学校省级质量工程项目(2023sx090);校企融合发展“恒瑞科研基金”横向课题项目(XQHR202426);国家卫生健康委医院管理研究所医院药学高质量发展研究项目(NIHAYS2434)。

摘　　要：目的:探讨清络饮(Qing-Luo-Yin,QLY)经HIF-1α/VEGF通路治疗佐剂诱导关节炎(adjuvant-inducedarthritis,AIA)大鼠模型异常血管新生的基本机制。方法:SD大鼠诱导建立AIA模型后采用QLY浸膏连续灌胃治疗,观察关节病理变化;ELISA法检测血浆中HIF-1α、VEGF、PDGF、TGF-β1浓度;生化法检测血浆中MDA和SOD等水平。体外实验中,采用MTT法、细胞划痕实验和成管实验评价QLY的抗血管新生能力,并同步检测相关蛋白表达水平。结果:与对照组比较,AIA大鼠关节滑膜增生和血管新生明显,伴有HIF-1ɑ、VEGF、PDGF、TGF-β1水平上升,而MDA/SOD比例降低;QLY治疗后上述异常均得以缓解。体外QLY刺激HUVEC细胞,抑制了后者增殖、愈伤和成管能力,p-MEK/MEK、p-ERK/ERK及HIF-1α表达显著降低。结论:清络饮可能通过调控HIF-1α/VEGF信号通路抑制HUVEC细胞增殖、迁移和血管新生,减轻AIA组大鼠的氧化应激反应和血管翳形成。AIM:To investigate the involvement of HIF-1α/VEGF regulation in its anti-angiogenesis effects using adjuvant-induced arthritis(AIA)rats.METHODS:AIA rats were orally treated by QLY extract for 24 days.After sacrifice,the joints were subjected to histological examination,while the blood was used in ELISA or biochemical tests.In addition,HUVEC cells were treated by QLY in vitro.MTT,wound-healing and tube-formation experiments were then performed.Expression of some relevant proteins in cells were investigated.RESULTS:Compared to the healthy controls,obvious synovial invasion and angiogenesis occurred in AIA rats.Blood levels of HIF-1ɑ,VEGF,PDGF,and TGF-β1 were increased,while the ratio of MDA/SOD was decreased a lot.After QLY treatment,all these abnormalities were attenuated.In vitro experiments,QLY showed notable potentials in inhibiting proliferation,migration and tube-constructing abilities of HUVEC cells.Furthermore,it suppressed the expression of p-MEK/MEK and p-ERK/ERK.CONCLUSION:QLY can reduce the pathological functions of vascular endothelial cells by inhibiting HIF-1α/VEGF,and it consequently eased AIA-related abnormal angiogenesis in AIA rats'joints.

关 键 词：清络饮 类风湿关节炎 中药 痹证 滑膜炎 

分 类 号：R965.2[医药卫生—药理学]