Calcium channel blocker nilvadipine, but not diltiazem, inhibits ocular inflammation in endotoxin-induced uveitis
Calcium channel blocker nilvadipine, but not diltiazem, inhibits ocular inflammation in endotoxin-induced uveitis
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DOI：
10.1007/s10384-010-0862-5
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发表时间：
2010-11
影响因子：
2.4
通讯作者：
S. Ishida;Takashi Koto;N. Nagai;Y. Oike
中科院分区：
文献类型：
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作者：
S. Ishida;Takashi Koto;N. Nagai;Y. Oike
目的钙通道阻滞剂（CCBs）广泛应用于高血压患者，近年来发现其通过抗氧化作用抑制动脉粥样硬化。本研究的目的是检查是否CCBs尼伐地平和地尔硫卓减少眼内毒素诱导的葡萄膜炎（EIU）的炎症反应。MethodsEIU诱导雄性C57/B6小鼠与单次腹腔注射脂多糖（LPS）。在LPS应用前5天，动物接受尼伐地平、地尔硫卓或载体的腹膜内注射。EIU诱导后24小时，用伴刀豆球蛋白A凝集素灌注标记技术计数粘附于视网膜血管的白细胞。测量房水中的蛋白质浓度以评估血眼屏障破坏。采用酶联免疫吸附试验分析视网膜细胞间粘附分子（ICAM）-1和单核细胞趋化蛋白（MCP）-1的水平。LPS刺激产生的超氧化物在小鼠微血管内皮细胞进行了检查与硝基四氮唑蓝assay.ResultsCompared车辆treatment，应用尼伐地平，但不是地尔硫卓，导致显着抑制EIU相关的视网膜白细胞粘附，连同前房蛋白渗漏，视网膜表达的ICAM-1和MCP-1，结论CCB尼伐地平通过抑制炎症相关分子而对眼部炎症的发生具有抑制作用。
PurposeCalcium channel blockers (CCBs), widely used for hypertensive patients, have recently been shown to inhibit atherosclerosis by their antioxidative action. The aim of the present study was to examine whether the CCBs nilvadipine and diltiazem reduce ocular inflammation in endotoxin-induced uveitis (EIU).MethodsEIU was induced in male C57/B6 mice with a single intraperitoneal injection of lipopolysaccharide (LPS). The animals received intraperitoneal injections of either nilvadipine, diltiazem, or vehicle for 5 days before the LPS application. Twenty-four hours after EIU induction, adherent leukocytes to the retinal vasculature were counted with a concanavalin A lectin perfusion-labeling technique. The protein concentration in the aqueous humor was measured to assess blood-ocular barrier breakdown. Retinal levels of intercellular adhesion molecule (ICAM)-1 and monocyte chemotactic protein (MCP)-1 were analyzed by enzyme-linked immunosorbent assay. LPS-stimulated generation of superoxide in murine microvascular endothelial cells was examined with a nitroblue tetrazolium assay.ResultsCompared to vehicle treatment, application of nilvadipine, but not diltiazem, led to significant suppression of EIU-associated retinal leukocyte adhesion, together with anterior-chamber protein leakage, retinal expression of ICAM-1 and MCP-1, and LPS-induced superoxide generation in vitro.ConclusionsThe CCB nilvadipine exercises an inhibitory effect on the pathogenesis of ocular inflammation through the suppression of inflammation-related molecules.