国际眼科杂志
國際眼科雜誌
국제안과잡지
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
2008年
1期
6-9
,共4页
熊蕾%权颜龙%郑玉萍%张利敏%张璐琰%熊全臣
熊蕾%權顏龍%鄭玉萍%張利敏%張璐琰%熊全臣
웅뢰%권안룡%정옥평%장리민%장로염%웅전신
血小板源性生长因子%受体酪氨激酶%AG1295%AG1296%增殖性玻璃体视网膜病变
血小闆源性生長因子%受體酪氨激酶%AG1295%AG1296%增殖性玻璃體視網膜病變
혈소판원성생장인자%수체락안격매%AG1295%AG1296%증식성파리체시망막병변
platelet-derived growth factor%receptor tyrosine kinase%AG1295%AG1296%proliferative vitreore-tinopathy
目的 血小板源性生长因子(platelet-derived growth factor,PDGF)可引起增殖性玻璃体视网膜病变,本研究评价特异性的PDGF-a受体酪氨酸激酶阻断剂AG1295对兔PVR的治疗作用.方法 兔结膜成纤维细胞(rabbit conjunctical fibroblats,RCF)培养,用MTT法检测PDGF-AA和-BB以及AG1295和AG1296对兔RCF增殖状况的影响.眼视网膜电图检查和HE染色分析药物的毒性.建立PVR动物模型,玻璃体腔内分别给予AG1295和AG1296.用牵引性视网膜脱离(tractional ratinal detachment,TRD) 的发生率评价药物的体内疗效.结果 体外10umol/L的AG1295和AG1296和均可显著抑制由PDGF-AA和-BB诱导的成纤维细胞的增生,体内100umol/L AG1295和AG1296均减慢了兔TRD的发生,但AG1295的作用仅持续至14d.相同浓度的AG1296和AG1295相比,作用更持久.在两个治疗组中,均未发现明显的视网膜毒性.结论 特异性的PDGF-a受体酪氨酸激酶抑制剂AG1296可显著抑制兔TRD的发生,其作用明显强于PDGF-a受体酪氨激酶抑制AG1295,提示PDGF对PBR的促进作用主要由a受体介导,这一通路的阻断可能成为治疗PVR的一种方法.
目的 血小闆源性生長因子(platelet-derived growth factor,PDGF)可引起增殖性玻璃體視網膜病變,本研究評價特異性的PDGF-a受體酪氨痠激酶阻斷劑AG1295對兔PVR的治療作用.方法 兔結膜成纖維細胞(rabbit conjunctical fibroblats,RCF)培養,用MTT法檢測PDGF-AA和-BB以及AG1295和AG1296對兔RCF增殖狀況的影響.眼視網膜電圖檢查和HE染色分析藥物的毒性.建立PVR動物模型,玻璃體腔內分彆給予AG1295和AG1296.用牽引性視網膜脫離(tractional ratinal detachment,TRD) 的髮生率評價藥物的體內療效.結果 體外10umol/L的AG1295和AG1296和均可顯著抑製由PDGF-AA和-BB誘導的成纖維細胞的增生,體內100umol/L AG1295和AG1296均減慢瞭兔TRD的髮生,但AG1295的作用僅持續至14d.相同濃度的AG1296和AG1295相比,作用更持久.在兩箇治療組中,均未髮現明顯的視網膜毒性.結論 特異性的PDGF-a受體酪氨痠激酶抑製劑AG1296可顯著抑製兔TRD的髮生,其作用明顯彊于PDGF-a受體酪氨激酶抑製AG1295,提示PDGF對PBR的促進作用主要由a受體介導,這一通路的阻斷可能成為治療PVR的一種方法.
목적 혈소판원성생장인자(platelet-derived growth factor,PDGF)가인기증식성파리체시망막병변,본연구평개특이성적PDGF-a수체락안산격매조단제AG1295대토PVR적치료작용.방법 토결막성섬유세포(rabbit conjunctical fibroblats,RCF)배양,용MTT법검측PDGF-AA화-BB이급AG1295화AG1296대토RCF증식상황적영향.안시망막전도검사화HE염색분석약물적독성.건립PVR동물모형,파리체강내분별급여AG1295화AG1296.용견인성시망막탈리(tractional ratinal detachment,TRD) 적발생솔평개약물적체내료효.결과 체외10umol/L적AG1295화AG1296화균가현저억제유PDGF-AA화-BB유도적성섬유세포적증생,체내100umol/L AG1295화AG1296균감만료토TRD적발생,단AG1295적작용부지속지14d.상동농도적AG1296화AG1295상비,작용경지구.재량개치료조중,균미발현명현적시망막독성.결론 특이성적PDGF-a수체락안산격매억제제AG1296가현저억제토TRD적발생,기작용명현강우PDGF-a수체락안격매억제AG1295,제시PDGF대PBR적촉진작용주요유a수체개도,저일통로적조단가능성위치료PVR적일충방법.
AIM:Receptor tyrosine kinase (RTK) activation is critical for growth factor-mediated cell proliferation. The present study was designed to determine the effect of the tyrphostin AG1295 and AG1296, a selective blocker of PDGF βand αRTK,on proliferative vitreoretinopathy (PVR) development.
METHODS:Rabbit conjunctival fibroblasts (RCF) cells were cultured.The effects of AG1295, AG1296,PDGF-AA and PDGF-BB on RCF proliferation are evaluated by MTT assay.Homologous rabbit conjunctival fibroblasts were injected intravitreally to make animal PVR model, followed by injection of 100μmol/L of AG1295 or AG1296 respectively. The presence of tractional retinal detachment (TRD) was assessed to evaluate the effect of AG1295 and AG1296 in vivo .Electroretinography and histologic studies were performed after intravitreal injection of AG1295 into untreated eyes to evaluate toxicity.
RESULTS: Both AG1295 and AG1296 (10μmol/L) significantly inhibited rabbit conjunctival fibroblast cell growth stimulated by PDGF-AA or -BB in vitro.Development of TRD was significantly reduced (P<0.05) with 100 μmol/L of AG1295 or AG1296 in vivo, but the effect of AG1295 only present till day 14. Inhibitive effect of AG1296 is longer than that of AG1295.No significant histologic or retinal functional damage was found in both drug-treated groups.
CONCLUSION: PDGF αand βreceptor specific inhibitor AG1296 and AG1295 attenuated PVR without significant side effects in rabbits, and AG1296 was better than AG1295. The much longer and stronger therapeutic effect from PDGFαreceptor inhibitor indicated that PDGF α receptor is more important in the development of PVR, and inhibition of this pathway could be a useful treatment alternative to prevent PVR.
