负载5-氟尿嘧啶的PLGA微球抑制成纤维细胞增殖的实验研究  

Experimental study on inhibition of fibroblast proliferation by PLGA microspheres loaded with 5-fluorouracil

作　　者：吴国明[1] 张盈 王楠[1] WU Guoming;ZHANG Ying;WANG Nan(Department of Orthopedics,Jiangnan Hospital Affiliated to Zhejiang Chinese Medical University,Hangzhou 311201,China;Department of Gynecology t First People's Hospital of Xiaoshan District,Hangzhou 311201,China)

机构地区：[1]浙江中医药大学附属江南医院骨科,浙江杭州311201 [2]萧山区第一人民医院妇科,浙江杭州311201

出　　处：《健康研究》2022年第6期667-670,675,F0003,共6页Health Research

基　　金：萧山区重大科技计划项目(2018213)。

摘　　要：目的 探究负载5-氟尿嘧啶的聚乳酸-羟基乙酸共聚物(poly lactic-co-glycolic acid, PLGA)微球对成纤维细胞增殖和凋亡肌腱损伤的影响。方法 使用PLGA作为5-氟尿嘧啶载体材料试制负载5-氟尿嘧啶的PLGA(5-Fu-PLGA)微球缓释剂。在体外成纤维的细胞模型上,通过组合运用Western-blot、激光共聚焦扫描显微镜等一系列实验技术评估负载5-氟尿嘧啶对细胞凋亡及相关信号转导的影响。结果 成功制备5-Fu-PLGA微球。CCK-8检测结果显示,不同浓度的5-氟尿嘧啶的PLGA微球能够以剂量依赖性的方式抑制成纤维细胞的增殖;Western-blot检测结果显示,5-Fu-PLGA微球处理成纤维细胞后,AKT、Juk、mTOR及Bcl-2、Bcl-xL、Survivin的表达水平低于对照组,Bax、Bim的表达水平高于对照组,差异均有统计学意义(P<0.05)。与对照组比较,5-Fu-PLGA微球处理的成纤维细胞内ROS含量升高,5-氟尿嘧啶的PLGA微球引起成纤维细胞凋亡的比例显著提高,差异均有统计学意义(P<0.05)。结论 5-氟尿嘧啶的PLGA微球缓释剂能够显著抑制成纤维细胞的增殖,促进成纤维细胞凋亡。Objective To investigate the effects of poly lactic-co-glycolicacid(PLGA) microspheres loaded with 5-fluorouracil on fibroblast proliferation and apoptotic tendon injury. Methods PLGA(5-Fu-PLGA) microsphere sustained-release agent loaded with 5-fluorouracil was prepared using PLGA as carrier material of 5-fluorouracil. On the cell model of fibroblasts in vitro, a series of experimental techniques such as Western-blot and laser confocal scanning microscope were used to evaluate the effects of 5-fluorouracil loading on cell apoptosis and related signal transduction. Results 5-Fu-PLGA microspheres were successfully prepared. CCK-8 test results showed that PLGA microspheres with different concentrations of 5-fluorouracil could inhibit the proliferation of fibroblasts in a dose-dependent manner. Western blot test results showed that the expression levels of AKT, Juk, mTOR, Bcl-2, BclxL, and Survivin in fibroblasts treated with 5-Fu PLGA microspheres were lower than those in the control group, and the expression levels of Bax and Bim were higher than those in the control group. The differences were statistically significant(P<0.05). Compared with the control group, the ROS content in fibroblasts treated with 5-Fu-PLGA microspheres increased, and the proportion of fibroblasts apoptosis induced by 5-fluorouracil PLGA microspheres increased. The differences were statistically significant(P<0.05). Conclusions PLGA microspheres of 5-fluorouracil can significantly inhibit the proliferation of fibroblasts and promote apoptosis of fibroblasts.

关 键 词：聚乳酸-羟基乙酸共聚物 信号转导 成纤维细胞 肌腱粘连 细胞凋亡 

分 类 号：R622[医药卫生—整形外科]