α-硫辛酸对视网膜缺血-再灌注损伤大鼠视网膜中血管内皮生长因子和基质金属蛋白酶表达的影响  

Effects of α-lipoic acid on the expression of vascular endothelial growth factor and matrix metalloproteinase-9 in rat retinal ischemia/reperfusion injury

作　　者：张书[1] 张文芳[1] 鲁建华[1] 张金红[1] 梁丽[1] 

机构地区：[1]兰州大学第二医院眼科,730000

出　　处：《眼科研究》2010年第11期1042-1047,共6页Chinese Ophthalmic Research

摘　　要：目的探讨α-硫辛酸对大鼠视网膜缺血-再灌注损伤中血管内皮生长因子(VEGF)和基质金属蛋白酶-9(MMP-9)表达的影响及作用机制。方法按随机数字表法将78只SPF级健康成年Wistar大鼠分为正常对照组6只及α-硫辛酸组和缺血-再灌注组各36只。α-硫辛酸组和缺血-再灌注组根据再灌注时间的不同分为6、12、24、48h,3d和7d组。采用前房灌注生理盐水升高眼压的方法建立视网膜缺血-再灌注动物模型,其中α-硫辛酸组大鼠自造模前3d开始腹腔注射α-硫辛酸100mg/(kg.d),缺血-再灌注组大鼠以同样的方法注射等体积生理盐水。在上述时间点分别处死大鼠并摘除眼球,行苏木精-伊红染色评估各组大鼠在各时间点视网膜组织的结构变化;应用免疫组织化学法检测大鼠视网膜缺血-再灌注损伤后不同时间点视网膜组织中VEGF和MMP-9的表达,并对各组VEGF和MMP-9的表达量进行比较。结果缺血-再灌注组大鼠在再灌注后6h出现视网膜水肿和视网膜神经节细胞(RGCs)的轻度改变,随着时间的延长,RGCs的结构改变明显加重。α-硫辛酸组视网膜水肿和RGCs结构的异常变化过程同缺血-再灌注组,但程度较轻。实验前后正常对照组大鼠视网膜中未见VEGF的表达;缺血-再灌注组于再灌注后12h开始出现VEGF的表达,随着时间的延长VEGF表达逐渐增加,到再灌注后48h达到高峰。各时间点缺血-再灌注组和α-硫辛酸组VEGF在视网膜的表达水平明显高于正常对照组,差异均有统计学意义(P<0.05),但各时间点α-硫辛酸组VEGF在视网膜的表达水平明显低于缺血-再灌注组,差异均有统计学意义(P<0.05)。正常对照组大鼠视网膜未检测到MMP-9的表达;缺血-再灌注组在再灌注后6h可检测到MMP-9在视网膜中的表达,24h后其表达水平达到高峰。各时间点缺血-再灌注组MMP-9的表达明显高于正常对照组(P均<0.05),α-硫辛酸组视网膜中MMP-9的表达与缺血-再Background Researches showed that retinal ischemia is associated with oxidizing-induced the overexpression of vascular endothelial growth factor（VEGF）and matrix metalloprotelnase-9（MMP-9）in retina.α-Lipoic acid is proved being a anti-oxidant agent with the protection on retinal ischemia/reperfusion injury.ObjectiveThe aim of this study was to investigate the effect and mechanism of α-lipoic acid on the expression of VEGF and MMP-9 in retinal ischemia/reperfusion injury.MethodsRetinal ischemia/reperfusion injury models were established in 72 SPF Wistar rats by perfusing the normal salt solution into the anterior chamber from a container at a height of 150cm to elevate the intraocular pressure（IOP）to 110mmHg for 60 minutes and then return the normal retinal color.α-Lipoic acid of 100mg/kg was intraperitoneally injected once per day from 3 days prior to the establishment of models in 36 rats,and equivalent amount of normal salt solution was administered at the same method in other 36 models.Six normal Wistar rats were used as control group.Structural change of retina was examined by haematine-eosin staining under the light microscope.The expression levers of VEGF and MMP-9 in retina were detected at 6,12,24,48 hours,3 days and 7 days after ischemia/reperfusion by using immunohistochemistry.ResultsEdema of retina and structural abnormality in different layers were found in 6 hours after ischemia/reperfusion injury.Pyknosis of nucleus and vacuolar degeneration of RGCs were displayed 24 hours later in model group.The structure change of RGCs was more slight in α-lipoic acid group compared with models group.No VEGF positive cell was found in normal group.However,in model rats,the average absorbency value（A value）of VEGF positive cells was gradually enhanced from 6 hours through 7 days after ischemia/reperfusion injury with the peak in 48 hours,showing significant differences in various time points compared with normal control group（P0.05）,and the expressive level of VEGF was obviously lower in α

关 键 词：Α-硫辛酸 视网膜 缺血-再灌注损伤 血管内皮生长因子 基质金属蛋白酶 

分 类 号：R774.1[医药卫生—眼科]