D-α-生育酚调节蛋白激酶C活性对糖尿病视网膜病变的影响

Effect of D-α-tocopherol on diabetic retinopathy via regulating protein kinase C activity

目的 探讨蛋白激酶C(PKC)在糖尿病视网膜病变 (DR)中的作用和D α 生育酚对糖尿病视网膜毛细血管组织病理的影响。方法 实验大鼠分为 4组 :正常对照组 (C组 )、D α 生育酚处理的正常对照组 (T组 )、糖尿病组 (D组 )、D α 生育酚处理病鼠组 (DT组 )。血糖、HbA1c和D α 生育酚含量以及原位PKC、ATPase活性在处理后 6个月被检测 ,毛细血管床形态立体定量评估DR。结果病程 6个月时 ,D组大鼠深、浅层毛细血管呈现周细胞减少、基底膜增厚的特征性改变 ,成模 6个月后糖尿病大鼠视网膜PKC活性显著增高 >10 0 % ,D α 生育酚可阻止此升高。同一大鼠视网膜 ,D α 生育酚也可阻止糖尿病诱导的Na+ K+ ATPase和Ca2 + ATPase活力下降。D α 生育酚可显著改善糖尿病视网膜微血管周、内皮细胞截面积和深浅层毛细血管基底膜厚度 ,而对血糖、HbA1c无影响。结论糖尿病诱导的组织病理异常可能大部分由PKC介导 ,D α

Objective To explore the role of protein kinase C (PKC) in the pathogenesis of diabetic retinopathy (DR) and effect of D α tocopherol on the histopathology of retinal capillaries in diabetic rats. Methods The experimental rats were divided into four groups: control rats (group C), control rats treated by D α tocopherol (group T), diabetic rats (group D), diabetic rats treated by D α tocopherol (group DT). Blood glucose, HbA 1c , D α tocopherol level, in situ PKC activity and ATPase activity were measured 6 months after treatment, and DR was assessed by quantitative morphometry of capillary bed. Results Untreated diabetic rats showed the characteristic pericyte decrease and capillary basement membrane thickening in both the superficial and deep capillaries beds of retina after 6 months follow up. Diabetes of 6 month duration resulted in >100% elevation of PKC activity in the retina, and administration of D α tocopherol prevented the elevation of PKC activity and diabetes induced decrease of both Na + K + ATPase and Ca 2+ ATPase activities. D α tocopherol achieved a complete prevention of augmented pericyte and endothelial cell profile areas and basement membrane thickening in the superficial and deep capillaries bed of diabetic retina but had no effect on blood glucose and HbA 1c . Conclusion Diabetes induced histopathological abnormalities are mostly mediated by PKC. D α tocopherol reduces the ultrastructural lesions in retinal capillary bed induced by hyperglycemia.