西塔格利普丁不干扰视网膜内皮细胞中的VEGF-A信号传递 in vitro
Lucian Amthor1, Anja Jaeckle1, Juergen Kampmeier1
1Department of Ophthalmology, Ulm University Medical Center, Ulm, Germany.
概括
乙型糖尿病药物西塔格利普丁 (Sitagliptin) 损害了视网膜内皮细胞障碍物,独立于VEGF-A信号传递. 这种二乙酶-4抑制剂不会干扰糖尿病黄斑的抗VEGF疗法.
科学领域:
- 眼科医生 眼科 眼科
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 西塔格利普丁是一种二二基酶-4抑制剂,用于治疗2型糖尿病.
- 糖尿病性黄斑是用血管内皮生长因子 (VEGF) -A抑制剂治疗的.
- 西塔格利普丁对视网膜内皮细胞屏障的影响及其与抗VEGF治疗的相互作用是未知的.
研究的目的:
- 调查西塔格利普丁是否会干扰抗VEGF治疗.
- 为了确定VEGF-A是否参与西塔利普丁诱导的屏障功能障碍.
主要方法:
- 培养的牛视网膜内皮细胞 (iBREC) 用西塔格利普丁和/或蒂沃扎尼布 (VEGF受体2抑制剂) 治疗,有或没有VEGF-A.
- 用细胞指数测量细胞透率.
- 分析了紧结蛋白 (克劳丁-1,克劳丁-5,PLVAP) 的表达和VEGF-A的分泌.
主要成果:
- 西塔利普丁没有诱导VEGF-A分泌.
- 提沃桑尼布并没有预防西塔格利普丁诱导的屏障功能障碍或改变克劳丁-1表达.
- 由VEGF-A诱导的屏障功能障碍和Claudin-1变化被Tivozanib阻断,不受西塔利普丁的影响.
- 西塔利普丁治疗改变了克劳丁-5的表达,影响了PLVAP的表达.
结论:
- 西塔格利平和VEGF-A通过不同的独立机制诱导视网膜内皮细胞屏障功能障碍.
- 西塔利普丁不会干扰VEGF信号传递抑制剂在治疗VEGF-A依赖性屏障功能障碍时的疗效.
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