Departments of Ophthalmology, Kagawa University Faculty of Medicine, Kagawa, Japan.
Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3629-38. doi: 10.1167/iovs.09-4107. Epub 2010 Feb 17.
PURPOSE. To investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II antagonist against retinal ischemia-reperfusion injury in the rat retina. METHODS. Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg. Rats were treated with an ACE inhibitor (captopril), an angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), an AT2-R antagonist (PD123319), bradykinin, or a bradykinin B2 receptor antagonist (icatibant). At 7 days after the ischemia, retinal damage was evaluated. Immunohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of AT1-R. Dark-adapted full-field electroretinography (ERG) was also performed. RESULTS. Pretreatment with captopril or candesartan significantly inhibited the ischemic injury of the inner retina. However, PD123319, bradykinin, or icatibant did not reduce the ischemic damage. In control retinas, retinal vessels were positive for AT1-R. In contrast, 12 hours after ischemia, immunohistochemical analysis detected numerous AT1-R-positive cells in the inner retina in vehicle-treated rats. After ischemia, the production of ROS was detected in retinal cells. However, pretreatment with captopril or candesartan suppressed the production of ROS. On the seventh postoperative day, the amplitudes of the ERG b-waves were significantly lower in the vehicle group than in the groups pretreated with captopril or candesartan. CONCLUSIONS. The present findings demonstrate that ischemic damage promotes the expression of AT1-R in the inner retina. Both the ACE inhibitor and the AT1-R antagonist that were examined can block the stimulation of the AT1-R and attenuate the subsequent ischemic damage in the rat retina.
目的。研究血管紧张素转换酶（ACE）抑制剂和血管紧张素 II 拮抗剂对大鼠视网膜缺血再灌注损伤的作用。
方法。通过将眼内压升高至 130mmHg 来诱导视网膜缺血。用 ACE 抑制剂（卡托普利）、血管紧张素 II 型 1 受体（AT1-R）拮抗剂（坎地沙坦）、AT2-R 拮抗剂（PD123319）、缓激肽或缓激肽 B2 受体拮抗剂（依替巴肽）对大鼠进行治疗。在缺血后 7 天，评估视网膜损伤。用免疫组织化学和图像分析来测量活性氧（ROS）水平的变化和 AT1-R 的定位。还进行了暗适应全视野视网膜电图（ERG）检查。
结果。卡托普利或坎地沙坦预处理显著抑制了内视网膜的缺血性损伤。然而，PD123319、缓激肽或依替巴肽并没有减少缺血性损伤。在对照视网膜中，血管对 AT1-R 呈阳性。相比之下，在缺血 12 小时后，在 vehicle 处理的大鼠中，内视网膜中检测到大量 AT1-R 阳性细胞。缺血后，在视网膜细胞中检测到 ROS 的产生。然而，卡托普利或坎地沙坦预处理抑制了 ROS 的产生。在术后第 7 天，与卡托普利或坎地沙坦预处理组相比，vehicle 组的 ERG b 波振幅显著降低。
结论。本研究结果表明，缺血性损伤促进了内视网膜中 AT1-R 的表达。所检查的 ACE 抑制剂和 AT1-R 拮抗剂均能阻断 AT1-R 的刺激，并减轻大鼠视网膜随后的缺血性损伤。
