CAJ | 학술논문

目的探讨载5-氟尿嘧啶(5-FU)聚乳酸纳米微粒(5-FU-PLA-NPs)对体外培养的人眼球筋膜囊成纤维细胞的抑制作用.方法为实验研究.噻唑蓝(MTT)比色法检测不同剂量(0.1、1.0、10.0、100.0和1000.0 mg/L)的空载聚乳酸纳米微粒(PLA-NPs)在不同时间点(48和72 h)对人眼球筋膜囊成纤维细胞增殖的影响,MTT比色法检测不同剂最(0.1、1.0、10.0、100.0和1000.0 mg/L)5-FU纳米药物和5-FU原药在1～7 d内共7个时间点对成纤维细胞生长的抑制作用,计算并比较两者在7个时间点对成纤维细胞的抑制率.RT-PCR分别检测剂量为100.0 mg/L的5-FU纳米药物和5-FU原药作用成纤维细胞1、5、7 d后Ⅲ型前胶原蛋白mRNA的表达情况.对同一天各浓度A值的比较用单因素方差分析,同一天相同浓度5-FU原药组A值与5-Fu-PLA-NPs组A值的比较用两独立样本t检验分析,采用单因素方差分析分别比较不同时间点各组COI3的相对A值.结果空载聚乳酸纳米微粒对成纤维细胞的增殖没有影响.载5-FU纳米微粒和5-FU原药均抑制成纤维细胞的增殖,并使Ⅲ型前胶原蛋白mRNA的表达水平降低,该抑制作用具有时间和剂量依赖性.作用初期各剂量组5-FU纳米微粒的抑制作用低于原药,随时间延长抑制作用超过原药,差异有统计学意义(P<0.05).结论聚乳酸(PEA)具有良好的生物相容性与安全性,可作为眼部用药的载体.载5-FU聚乳酸纳米微粒具有一定的缓释功能,可长期释放药物,随着作用时间的延长,5-FU纳米药物对成纤维细胞的抑制作用超过原药,其可作为靶向缓释药物载体.(中华眼科杂志,2009,45:26-31)
목적 탐토재5-불뇨밀정(5-FU)취유산납미미립(5-FU-PLA-NPs)대체외배양적인안구근막낭성섬유세포적억제작용.방법 위실험연구.새서람(MTT)비색법검측불동제량(0.1、1.0、10.0、100.0화1000.0 mg/L)적공재취유산납미미립(PLA-NPs)재불동시간점(48화72 h)대인안구근막낭성섬유세포증식적영향,MTT비색법검측불동제최(0.1、1.0、10.0、100.0화1000.0 mg/L)5-FU납미약물화5-FU원약재1～7 d내공7개시간점대성섬유세포생장적억제작용,계산병비교량자재7개시간점대성섬유세포적억제솔.RT-PCR분별검측제량위100.0 mg/L적5-FU납미약물화5-FU원약작용성섬유세포1、5、7 d후Ⅲ형전효원단백mRNA적표체정황.대동일천각농도A치적비교용단인소방차분석,동일천상동농도5-FU원약조A치여5-Fu-PLA-NPs조A치적비교용량독립양본t검험분석,채용단인소방차분석분별비교불동시간점각조COI3적상대A치.결과 공재취유산납미미립대성섬유세포적증식몰유영향.재5-FU납미미립화5-FU원약균억제성섬유세포적증식,병사Ⅲ형전효원단백mRNA적표체수평강저,해억제작용구유시간화제량의뢰성.작용초기각제량조5-FU납미미립적억제작용저우원약,수시간연장억제작용초과원약,차이유통계학의의(P<0.05).결론 취유산(PEA)구유량호적생물상용성여안전성,가작위안부용약적재체.재5-FU취유산납미미립구유일정적완석공능,가장기석방약물,수착작용시간적연장,5-FU납미약물대성섬유세포적억제작용초과원약,기가작위파향완석약물재체.(중화안과잡지,2009,45:26-31)
Objective To investigate the inhibitive effects of 5-fluorouracil-loaded polylactic acid nanoparticles (5-FU-PLA-NPs)on human Tenon's capsule fibroblasts in vitro. Methods This paper was experimental study. MTT assay was performed to estimate the effects of 0.1 mg/L, 1.0 mg/L, 10.0 mg/L, 100.0 mg/L, 1000.0 mg/L unloaded polylactic acid nanoparticles(PLA-NPs) on fibroblasts proliferation on 48 h, 72 h. MTT assay was performed to estimate the effects of 0.1 mg/L, 1.0 mg/L, 10. 0 mg/L, 100.0 mg/L, 1000.0 mg/L original 5-FU and 5-FU-PLA-NPs on fibroblasts' proliferation on 7 consecutive days respectively. The inhibitory rate of the two drugs against the fibroblasts was calculated. Cells were exposed to 100 mg/L original 5-FU and 5-FU-PLA-NPs respectively for 7 days. Semi-quantitative RT-PCR was used to observe the mRNA expression of type Ⅲ procollagen at the 1st day, 5th day and 7th day. Results PLA-NPs had no cytotoxicity on the fibroblasts. Both 5-FU-PLA-NPs and original 5-FU could inhibit the proliferation of the fibroblasts and make the expression of type Ⅲ procollagen mRNA lower in dose-dependent and time-dependent manner. The inhibitive effect of original 5-FU was more effective than 5-FU-PLA-NPs in the initial period, but the inhibitive effect of 5-FU-PLA-NPs was more effective than original 5-FU in long time. Conclusion PLA has good biocompatibility and safety, and can be used as a carrier of ophthalmic drags. 5-FU-PLA-NPs shows slow-releasing function. 5-FU-PLA-NPs can be proposed as a potential controlled and targeted ophthalmic delivery system for the treatment of antifibrosis after glaucoma filtering surgery. (Chin J Ophthalmol, 2009,45:26-31)