RESEACH FOR THE PATHOGENESIS OF DIABETIC RETINOPATHY

探讨葡萄糖诱导视网膜周细胞凋亡的机制，探讨糖尿病视网膜病变的发病机制。与5.5 mM葡萄糖条件下相比，20 mM葡萄糖条件下细胞内钙离子浓度和caspase-3活性显著升高，还原型谷胱甘肽含量和PKC活性显著降低。这些异常都被醛糖还原酶抑制剂SNK-860显著阻止。钙蛋白酶抑制剂SNK-860或还原型谷胱甘肽可部分但显著地阻止葡萄糖诱导的细胞凋亡，并被caspase-3抑制剂完全恢复正常。这些观察结果表明，葡萄糖诱导的视网膜周细胞凋亡可能是通过醛糖还原酶敏感的途径介导的，包括钙-钙蛋白酶级联、氧化应激增加和PKC活性降低，而caspase-3可能位于这些凋亡信号的最下游。

The mechanisms of the glucose-induced apoptosis in retinal pericytes were investigated to evaluate the pathogenesis of diabetic retinopathy. Under the 20 mM glucose condition, intracellular calcium concentrations and caspase-3 activities were significantly increased, and reduced glutathione contents and PKC activities were significantly decreased, compared with those under the 5. 5 mM glucose condition. These abnormalities were all significantly prevented by an aldose reductase inhibitor, SNK-860. Glucose-induced apoptosis was partially but significantly prevented by SNK-860, a calpain inhibitor, or reduced glutathione supplementation, and completely normalized by a caspase-3 inhibitor. These observations suggest that glucose-induced apoptosis in retinal pericytes would be mediated through an aldose reductase sensitive pathway including caicium-calpain cascade, increased oxidative stress and decreased PKC activities, and that caspase-3 would be located furthest down stream of these apoptotic signals.