Hirose Fumitaka, Kiryu Junichi, Miyamoto Kazuaki, Nishijima Kazuaki, Miyahara Shinsuke, Katsuta Hideto, Tamura Hiroshi, Honda Yoshihito
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hypertension. 2004 May;43(5):1098-102. doi: 10.1161/01.HYP.0000123069.02156.8a. Epub 2004 Mar 8.
A number of studies have suggested that hypertension affects the pathogenesis of inflammatory reactions in various organs. The objective of this study was to evaluate the effects of hypertension on leukocyte-endothelial interactions after transient retinal ischemia. Transient retinal ischemia was induced for 60 minutes in spontaneously hypertensive rats (SHR) and in age-matched normotensive Wistar-Kyoto rats (WKY). At 4, 12, 24, 48, and 72 hours after reperfusion, flat-mount retinas were prepared to evaluate the density of leukocytes that had been accumulated in the retina. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression was studied by semiquantitative polymerase chain reaction and ICAM-1 protein levels were studied by enzyme-linked immunosorbent assay. At 14 days after reperfusion, the retinal damage and the effect of superoxide dismutase on the damage were evaluated histologically. In SHR, the number of accumulated leukocytes peaked at 48 hours after reperfusion, and it was upregulated to 5.2-fold, as compared with that of WKY (P<0.001). ICAM-1 mRNA expression and ICAM-1 protein levels were increased significantly in the ischemia-reperfused retina in SHR compared with WKY (P<0.05). Histological examination demonstrated marked increase in the retinal ischemia/reperfusion damage in SHR (P<0.01) and a significant amelioration of the damage by treatment with superoxide dismutase in SHR (P<0.05). Oxidative stress may thus be an important mechanism for the deterioration seen in ischemia/reperfusion injury in the SHR retina.
多项研究表明,高血压会影响各器官炎症反应的发病机制。本研究的目的是评估高血压对短暂性视网膜缺血后白细胞与内皮细胞相互作用的影响。对自发性高血压大鼠(SHR)和年龄匹配的正常血压Wistar-Kyoto大鼠(WKY)进行60分钟的短暂性视网膜缺血诱导。在再灌注后4、12、24、48和72小时,制备视网膜铺片以评估视网膜中积聚的白细胞密度。通过半定量聚合酶链反应研究细胞间黏附分子-1(ICAM-1)mRNA表达,并通过酶联免疫吸附测定研究ICAM-1蛋白水平。在再灌注后14天,通过组织学评估视网膜损伤以及超氧化物歧化酶对损伤的影响。在SHR中,再灌注后48小时积聚的白细胞数量达到峰值,与WKY相比上调至5.2倍(P<0.001)。与WKY相比,SHR缺血再灌注视网膜中ICAM-1 mRNA表达和ICAM-1蛋白水平显著增加(P<0.05)。组织学检查显示SHR中视网膜缺血/再灌注损伤明显增加(P<0.01),并且SHR中用超氧化物歧化酶治疗可显著改善损伤(P<0.05)。因此,氧化应激可能是SHR视网膜缺血/再灌注损伤恶化的重要机制。