Attenuation of diabetes-induced retinal vasoconstriction by a thromboxane receptor antagonist.

Retinal blood flow has been reported to decrease early in human diabetes as well as in diabetic animal models. The purpose of the present study is to investigate the role of thromboxane receptor binding in the decrease of flow. C57BL/6 mice were injected with streptozotocin (STZ) at 11–12 weeks of age and remained hyperglycemic for 4 weeks. The mice were treated with a selective thromboxane receptor antagonist, GR32191B (vapiprost), in drinking water for the final three weeks at a dose of 1 mg/kg/day. In separate experiments, vapiprost was administered only once, as an acute injection 25 minutes prior to the experimental measurements. The measurements included retinal arteriolar and venular diameters and red blood cell (RBC) velocities, from which retinal blood flow was calculated. STZ induced decreases in vascular diameters and RBC velocities, resulting in an approximate 30% decrease in overall retinal blood flow. However, these decreases were not seen in mice given the three-week administration of vapiprost. Acute administration to diabetic mice of 1 mg/kg vapiprost, but not 0.1 mg/kg, induced arteriolar vasodilation, with the dilation more substantial in smaller feed arterioles. In summary, STZ-induced decreases in retinal blood flow can be attenuated by the thromboxane receptor antagonist vapiprost.

据报道，在人类糖尿病早期以及糖尿病动物模型中，视网膜血流会减少。本研究的目的是探讨血栓素受体结合在血流减少中的作用。11 - 12周龄的C57BL/6小鼠注射链脲佐菌素（STZ），并持续高血糖4周。在最后3周，小鼠通过饮用水接受选择性血栓素受体拮抗剂GR32191B（伐哌前列素）治疗，剂量为1mg/kg/天。在单独的实验中，伐哌前列素仅给药一次，即在实验测量前25分钟急性注射。测量包括视网膜小动脉和小静脉直径以及红细胞（RBC）流速，并据此计算视网膜血流。STZ导致血管直径和红细胞流速降低，使视网膜整体血流减少约30%。然而，在接受伐哌前列素3周给药的小鼠中未观察到这些降低情况。对糖尿病小鼠急性给予1mg/kg伐哌前列素（而非0.1mg/kg）可诱导小动脉血管舒张，在较小的分支小动脉中舒张更为显著。总之，血栓素受体拮抗剂伐哌前列素可减轻STZ诱导的视网膜血流减少。