摘要
目的通过检测糖基化终产物(AGE)诱导培养的牛视网膜毛细血管周细胞凋亡及凋亡周细胞中超氧化物歧化酶(SOD)的活性及意义,进一步探讨糖尿病视网膜病变(DR)的发生机制。方法周细胞分别与不同浓度的AGE(0.47、1.88、7.5μmol/L)共同培养4d后,分别检测细胞凋亡、SOD活性,以及SOD对细胞凋亡及凋亡调节基因Bcl-2/Bax比率的影响。结果AGE能以浓度依赖的方式诱导周细胞凋亡(r=0.878,P<0.01)、降低细胞内SOD的活性(r=-0.878,P<0.01),而应用SOD能明显抑制AGE作用下的周细胞凋亡及提高凋亡调节基因Bcl-2/Bax的比率。结论凋亡及氧化应激的增加是DRP中周细胞选择性丧失的主要原因,SOD活性的下降是AGE诱导周细胞发生凋亡的关键因素。
Objective One of the earliest changes observed in retinal microvcssels in diabetic retinopathy is the selective loss of intramural perieytes. Our previous study was to investigate cellular oxygenic metabolism,but the relationship of superoxide dismutase （SOD） ,a critical enzyme in maintaining cellular oxygenic metabolizing balance, with pericytes apoptosis has not been reported. We investigated the activity of SOD by detecting advanced glyeation end products（AGE） , which might be involved in the disappearance of retinal perieytes. Methods Cultured bovine retinal microvascular perieytes （BRPs） were exposed to various concentrations of advanced glycation end products （0.47,1.88,7.5 μmol/L） for 4 days. The pericytes apoptosis was assayed by fluorescence activated cell sorting （FACS） ,and the SOD activity and the effect of SOD on apoptosis and Bcl-2/Bax ratio were further measured. Results The results showed that the BRPs apoptosis was induced significantly by AGE in a dose-dependent manner compared with controls （ r = 0. 878, P 〈 0. 01 ）. Apoptosis of BRPs was negatively correlated with a decrease of intracellular SOD activity （ r = - 0. 878 ,P 〈 0.01 ）. 20 U/L SOD could reduce AGE-induced apoptosis by 47% and increase the Bcl-2/Bax ratio by 25% and 72% （ at the concentrations of AGE 0.47 μmol/L and 7.5 μmol/L respectively）. Conclusion the perlcyte loss in diabetic retinopathy is involved in an apoptotie induction and the reduction of SOD is associated with apoplosis of BRPs. These results provide new therapeutic approach to diabetic retinopathy.
出处
《眼科研究》
CSCD
北大核心
2007年第5期321-324,共4页
Chinese Ophthalmic Research
基金
湖南省科技厅科技计划项目(05FJ3067)
湖南省优秀博士论文专项基金(1341710080000)资助
