目的:观察缺氧诱导因子-1α(HIF-1α)在大鼠急性高眼压后血-视网膜屏障(BRB)损伤中的作用。方法:大鼠随机分为正常对照组、假手术组和急性高眼压组。用免疫组织化学检测视网膜HIF-1α的表达;用分光光度计定量视网膜伊文思蓝(EB)的含量;给予HIF-1α抑制剂2-甲氧基雌二醇(2ME2)干预后再次检测视网膜HIF-1α的表达和定量视网膜EB的含量。结果:HIF-1α免疫组织化学结果显示视网膜HIF-1α在对照组未见阳性表达,在急性高眼压后3h HIF-1α阳性产物增多,12h时达高峰,然后逐渐减少;在3h和1d时视网膜周围部HIF-1α阳性产物明显比中央部多;各时间点HIF-1α阳性产物主要见于节细胞层,3h和12h HIF-1α阳性表达物还见于内核层。EB定量结果显示急性高眼压后的早期BRB已经受破坏,之后逐渐恢复,而且存在部位差异。2ME2干预后,免疫组织化学和EB定量显示在相同时间点、相同部位视网膜的HIF-1α表达以及EB渗漏量均明显减少。结论:急性高眼压后大鼠视网膜HIF-1α的上调促进了血-视网膜屏障损伤。
Objective: To observe the role of hypoxia-inducible factor-1α (HIF-1α) on the blood-retinal barriers (BRB) damage after acute high intraocular pressure (AHIOP) in rat retina. Methods: The rats were randomly divided into a control group, a sham group and an AHIOP group. The rats survived for 3 h, 12 h, 1 d, 3 d and 7 d following AHIOP. The Evans blue (EB) content of retina was measured by spectrophotometer. HIF--1α protein was detected by immunohistochemistry. After 2-methoxyestradiol (2ME2), the HIF-1α inhibitor treatment, retinal HIF-1α expression and the content of the EB were detected again. Results: EB quantitation showed the EB content of the central retina began to increase in 3 h, and reached its peak in 12 h, and then gradually decreased. Most of EB leakage in the peripheral retina was found in 3 h, and then gradually decreased. Immunohistochemistry showed no positive HIF-1α expression in the control group. HIF-1α expression was up-regulated in 3 h and reached its peak in 12 h, and then gradually decreased. HIF-1α positive products were mainly distributed in the ganglion cell layer, and also found in the inner nuclear layer in 3 h and 12 h. After giving the 2ME2, the expressions of HIF-1α and EB content in the retina were significantly reduced in the corresponding time points and corresponding parts. Conclusion: Up-regulation of HIF-1α in the rat retina after AHIOP may promote the BRB damage.