花青素对晶状体上皮细胞氧化应激损伤和上皮间充质转化的抑制作用

Inhibitory effects of anthocyanin on oxidative stress injury and epithelial-mesenchymal transition of human lens epithelial cells

花青素(anthocyanin)是广泛存在于植物中的一种水溶性黄酮类色素。研究表明花青素对视力具有一定的保护作用,但其对于白内障是否具有治疗作用及机制尚不明确。本研究分别采用过氧化氢(hydrogen peroxide,H_2O_2)及转化生长因子-β_2(transforming growth factorβ_2,TGF-β_2)处理人晶状体上皮细胞(human lens epithelial cells,HLECs),诱导氧化应激损伤及上皮-间充质转化(epithelial-mesenchymal transition,EMT),以构建年龄相关性白内障(age-related cataract,ARC)及后囊膜浑浊型白内障(posterior capsule opacification,PCO)细胞模型,并检测花青素对HLECs氧化应激损伤及EMT标志物的影响。结果表明,花青素有较好的抗氧化应激损伤作用,能明显保护细胞活力,增加细胞内SOD、GSSG、GSH-Px及α-晶状体蛋白水平,降低细胞内MDA、ROS及Ca^(2+)水平;同时,花青素显著抑制后囊膜浑浊型白内障发生发展的病理进程,能明显抑制TGF-β_2诱导的HLECs增殖、迁移,降低EMT标志物COL1A1、COL1A2、COL3、COL4、Fn、α-SMA的m RNA表达水平。综上,花青素能保护HLECs细胞对抗H_2O_2诱导的自由基损伤及由TGF-β_2诱导的EMT,对ARC及PCO具有一定的预防和治疗作用。

Anthocyanin is a water-soluble flavonoid pigment which is widely found in plants. Studies showed that anthocyanin had protective effect on vision. However, whether anthocyanin has therapeutic effect on cataract remain unclear. In this study, we established the age-related and posterior capsule opacification cataract cell models through inducing oxidative damage of human lens epithelial cells （HLECs） by H2O2 and inducing epithelial-mesenchymal transition （EMT） by transforming growth factor β2 （TGF-β2）. The preventative effects of anthocyanin on markers of oxidative damage and EMT were determined by respective assay kits and PCR analysis. Anthocyanin was beneficial to reduce oxidative stress of HLECs, protecting cells from H2O2 induced damage and increasing α-crystallin expression. The potential mechanisms might be that anthocyanin increased the activities of SOD and GSH-Px, which contributes to reduce cellular ROS and MDA level. Besides, anthocyanin inhibited Ca^2＋ overload, which contributes to protection of cell from apoptosis. Meanwhile, anthocyanin had inhibitory effect on EMT, slowed down cell proliferation, migration caused by TGF-β2 through decreasing mRNA expression levels of EMT markers including COL1A1, COL1A2, COL3, COL4, Fn and α-SMA. The results suggest that anthocyanin could protect HLECs from oxidative damage induced by H2O2 and cell proliferation, migration and EMT induced by TGF-β2, which indicated that anthocyanin may have protective and therapeutic effects on age-related cataract and posterior capsule opacification.