急性心肌缺血诱发视网膜P物质表达变化及其机制

Expression of substance P in retina following coronary artery occlusion in rats

目的观察分析机体应激反应状态下视网膜组织内P物质表达的变化,探讨全身因素与视网膜炎症性改变的关系。方法采用结扎冠状动脉左前降支的方法制备SD大鼠急性心肌缺血模型。将153只(306只眼)健康成年雄性SD大鼠随机分为11个组(免疫组织化学实验:6只眼/组;酶联免疫吸附实验:48只眼/组):正常对照组(C组);假手术0.5、1、3、6h组;结扎冠状动脉(CAO)0.5、1、3、6h组;药物干预组:酚妥拉明组和艾司洛尔组。各组在预定时间点迅速摘除眼球制作标本。采用免疫组织化学法和酶联免疫吸附法观察各组大鼠视网膜内P物质的表达情况。结果CAO各时间点组P物质表达水平较C组均有升高(P<0.05),CAO3h时P物质表达达峰值(P<0.05);CAO各时间点组P物质表达水平较假手术相应时间点组显著升高(P<0.05);药物干预组P物质表达水平较CAO组下降(P<0.05)。结论结扎冠状动脉可诱发神经源性应激反应,导致大鼠视网膜内P物质表达水平升高;肾上腺素能机制参与介导上调P物质表达。

Objective The aim of this study was to investigate the potential association between neurogenic stress and pathological change of retina by exploring the change of substance P in retina following acute myocardial ischemic stress induced by coronary artery occlusion, and study the effects of antagonists of α-adrenergic and β-adrenergic receptors on the up - regulation of the expression of SP. Methods Total 153 Sprague-Dawley rats were used in this study. The acute myocardial ischemia model was established by ligating the left anterior descending branch of coronary artery in male Sprague-Dawley rats. Only chest cavity was incised in rats in sham surgery group. Normal rats were as control group. Rigitine or esmolol was injected via caudal vein 15 minutes prior to coronary artery occluding in rats of rigitine group or esmolol group respectively. The animals were sacrificed and eyeballs were enucleated in 0.5 hours, 1 hour,3 and 6ours after operation for the detect of substance P in retina by immunochemistry and EIA. Results Retinal edema and retinal structural disorder were more prominent at 3 hours after coronary artery ligation under the optical microscope. Immunochemistry showed that the substance P was expressed in inner nuclear laye and retinal ganglion cell layer in normal control group, and the positive granula for substance P in retina was significantly increased from 0.5 hours through 6 hours after ligation of coronary artery. The semiquantitative and EIA study showed that the expression level of substance P was significantly increased in coronary artery ligation group compared with control group （P 〈 0. 05）. In sham group compared with coronary artery occluding group, the expression level of substance P was significantly decreased at various time points（P 〈 0.05 ）. The positive reactive level of substance P was considerably reduced in pre-intervene groups of rigitine and esmolol （ P 〈 0.05 ）. Conclusion The stress evoked by acute myocardial ischemia could cause up-regulation of expression of SP and the effect is likely to be mediated by adrenergic mechanism. Rigitine and esmolol can attenuate the up-regulation of expression of substance P in retina.