α-硫辛酸对大鼠视网膜缺血再灌注损伤中VEGF、MMP-9表达的影响

发布时间：2018-08-08 11:08

【摘要】： 目的探讨α-硫辛酸对大鼠视网膜缺血再灌注损伤(retinal ischemia/reperfusion injury,RIRI)中血管内皮生长因子(vascular endothelial growth factor,VEGF)和基质金属蛋白酶-9(matrix metalloprotelnase-9,MMP-9)表达的影响及作用机制。方法按随机分组的原则将78只健康成年Wistar大鼠分为正常对照组6只,α-硫辛酸治疗组(造模前3d开始腹腔注射α-辛酸注射液100mg·kg-1,每天1次,直至处死)和缺血组(造模前3d开始腹腔注射等量生理盐水,每天1次,直至处死)各36只。采用生理盐水前房灌注升高眼内压的方法建立视网膜缺血再灌注模型,维持眼内压110mmHg,持续60分钟后拔出灌注针头。分别于视网膜缺血再灌注后6h、12h、24h、48h、3d和7d处死大鼠,HE染色光镜观察视网膜组织变化,应用免疫组织化学法检测大鼠视网膜缺血再灌注损伤后视网膜组织VEGF和MMP-9表达的变化。结果视网膜缺血再灌注后早期,视网膜内层水肿增厚,晚期视网膜神经节细胞数目减少及视神经纤维层萎缩变薄。α-硫辛酸治疗组组织变化趋势与缺血组相似,细胞数目减少及视网膜厚度变薄的程度均较缺血组有明显改善。正常对照组未观察到明显VEGF和MMP-9的表达(AOD分别为0.06±0.04和0.05±0.03)。缺血组和α-硫辛酸治疗组在再灌注后12小时开始出现VEGF的明显表达,并逐渐增加,到再灌注后48小时达到高峰(AOD分别为0.52±0.06和0.35±0.05), MMP-9的表达自再灌注后6小时开始增加,24小时后达到高峰(AOD分别为0.38±0.06和0.29±0.05)。除了再灌注后6小时VEGF的表达外,其余各时间段缺血组VEGF、MMP-9的表达与正常对照组比较有统计学差异(P0.05), a-硫辛酸治疗组与缺血再灌注组比较差异有统计学意义(P0.05)。经相关性分析发现,缺血组视网膜VEGF和MMP-9的表达呈正相关(r=0.834, P0.05)。结论α-硫辛酸对RIRI有保护作用,可能通过抑制了RIRI中VEGF及MMP-9的表达而发挥作用。
[Abstract]:Objective to investigate the effect of 伪 -lipoic acid on the expression of vascular endothelial growth factor (vascular endothelial growth) and matrix metalloproteinase-9 (matrix metalloproteinase-9) in retinal ischemia/reperfusion injury-reperfusion injury in rats. Methods Seventy-eight healthy adult Wistar rats were randomly divided into normal control group (n = 6). 伪 -lipoic acid injection (100mg kg-1) was injected intraperitoneally 3 days before modeling. There were 36 rats in the ischemic group and 36 rats in the ischemic group (36 rats in each group were given intraperitoneal injection of the same amount of normal saline once a day until the death) 3 days before the model was made. The model of retinal ischemia-reperfusion was established by using normal saline anterior chamber perfusion to increase intraocular pressure. The intraocular pressure was maintained at 110 mm Hg.After 60 minutes, the perfusion needle was pulled out. The changes of retinal tissue were observed by HE staining at 6 h, 12 h, 24 h and 48 h, respectively, and the expression of VEGF and MMP-9 in retinal tissue of rats after retinal ischemia-reperfusion injury were detected by immunohistochemical method. Results in the early stage of retinal ischemia reperfusion, the thickness of retinal inner layer edema increased, the number of retinal ganglion cells decreased and the optic nerve fiber layer shrunk in late stage. The change trend of 伪 -lipoic acid treatment group was similar to that of ischemic group. The decrease in the number of cells and the thickness of retina were significantly improved compared with the ischemic group. No significant expression of VEGF and MMP-9 was observed in normal control group (AOD was 0.06 卤0.04 and 0.05 卤0.03, respectively). In ischemia group and 伪 -lipoic acid treatment group, the expression of VEGF began to appear 12 hours after reperfusion, and increased gradually. The expression of MMP-9 reached its peak at 48 hours after reperfusion (AOD was 0.52 卤0.06 and 0.35 卤0.05, respectively), and the expression of MMP-9 reached its peak at 24 hours after reperfusion (AOD was 0.38 卤0.06 and 0.29 卤0.05, respectively). In addition to the expression of VEGF at 6 hours after reperfusion, the expression of VEGF MMP-9 in ischemic group was significantly different from that in normal control group (P0.05), and there was a significant difference between a-lipoic acid treatment group and ischemia-reperfusion group (P0.05). The expression of VEGF and MMP-9 was positively correlated in ischemic group (r = 0.834, P 0.05). Conclusion 伪 -lipoic acid can protect RIRI by inhibiting the expression of VEGF and MMP-9 in RIRI.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R774.1

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