维生素A对糖基化终末产物诱导的角膜上皮细胞损伤的作用及机制研究

目的糖基化终末产物(AGEs)在糖尿病患者在角膜外伤或接受角膜手术时极易出现角膜上皮愈合延迟甚至不愈的过程中起着关键作用,本文研究维生素A(VA)对以糖基化终末产物AGE-BSA诱导角膜上皮细胞损伤的影响及可能的作用机制。方法以HCE-2细胞为研究对象,AGE-BSA为诱导剂,试剂盒检测VA对细胞凋亡率及线粒体膜电位的影响,荧光显微镜检测细胞内凋亡小体,Western blot检测相关的蛋白表达量。结果VA抑制AGE-BSA诱导的HCE细胞凋亡,调节AGEBSA引起的凋亡相关蛋白的变化。同时,VA与JNK的抑制剂同等程度的减少AGE-BSA诱导的JNK和NF-κB的磷酸化。结论VA可能通过抑制JNK介导的NF-κB炎症通路而起到减少AGE-BSA诱导的角膜上皮细胞凋亡的作用,可以作为糖尿病患者角膜上皮损伤的保护剂。

Effects and the Underlying Mechanism of Vitamin A(VA)Against Damage Induced by Advanced Glycation End Products(AGEs)

OBJECTIVE Advanced Glycation End Products(AGEs)has been implicated in the progression of diabetic keratopathy.In the current study,we focused on the protective effects and the underlying mechanism of vitamin A(VA)against damage induced by AGE-modified bovine serum albumin(AGE-BSA).METHODS We used AGE-BSA as inducer to assess the protective effects of VA.Apoptosis of cells was measured with Annexin V Apoptosis and Necrosis Assay kit and Hoechst 33342-based fluorescence microscopy.Mitochondrial membrane potential was also measured using commercial kits.Protein levels were detected using Western blot.RESULTS VA reduced AGE-BSA-induced HCE-2 cells apoptosis and Bax/Bcl-2 ratio.Additionally,VA inhibited JNK and NF-kB activation as that of the JNK inhibitor.CONCLUSION VA inhibits AGE-BSA induced corneal epithelial cells apoptosis by JNK mediated NF-kB activation and it may become a promising drug for treatment of the corneal epithelial disorders of diabetic patients.