CD147、基质金属蛋白酶-2和血管内皮生长因子在氧诱导视网膜病变大鼠中的表达

目的 观察CD147、基质金属蛋白酶（MMP）-2和血管内皮生长因子（VEGF）在氧诱导视网膜病变大鼠中的表达。方法 84只新生Wistar大鼠纳入研究。将其随机分为高氧组和对照组。每组42只大鼠。高氧组建立氧诱导视网膜病变模型；对照组不做任何处理。大鼠7、14日龄时，取眼球行视网膜铺片，观察视网膜血管形态。大鼠14日龄时，取眼球行视网膜石蜡切片，计数突破内界膜的内皮细胞核数。大鼠12、14、16日龄时，取眼球行免疫组织化学染色，检测大鼠视网膜组织中CD147、MMP-2和VEGF的表达。采用双因素相关分析法分析CD147表达与MMP-2、VEGF表达的相关性。结果 大鼠7日龄时，对照组大鼠视网膜血管呈放射状分布，血管径较粗；高氧组大鼠视网膜血管收缩，大面积无血管区，仅见少量小面积的血管网。大鼠14日龄时，对照组大鼠视网膜血管发育较好，网格规整；高氧组大鼠视网膜血管增生、纡曲、扩张，并在灌注区与非灌注区交界处形成新生血管丛、渗出、出血。大鼠14日龄时，对照组、高氧组突破内界膜的内皮细胞核数分别为（1.30±1.26）、（19.70±3.56）个；两组比较，差异有统计学意义（t=21.813，P＜0.01）。免疫组织化学染色结果显示，对照组大鼠视网膜各层可见CD147、MMP-2、VEGF有少量表达；高氧组大鼠视网膜各层可见CD147、MMP-2、VEGF有大量表达。大鼠12、14、16日龄时，两组大鼠视网膜各层中CD147（t=5.612、11.390、6.355）、MMP-2（t=4.122、8.047、4.422）、VEGF（t=4.955、12.176、5.110）表达比较，差异均有统计学意义（P＜0.01）。相关性分析发现，CD147的表达与MMP-2、VEGF的表达均呈正相关(r=0.755、0.820，P＜0.01）。 结论 CD147、VEGF、MMP-2在氧诱导视网膜病变大鼠中有大量表达。

The expression of CD147, matrix metalloproteinases-2 and vascular endothelial growth factor in a rat model of oxygen induced retinopathy

Objective To observe the expression of CD147, matrix metalloproteinases-2 (MMP-2) and vascular endothelial growth factor (VEGF) in a rat model of oxygen induced retinopathy (OIR). Methods Eighty-four neonatal Wistar rats were divided into two groups randomly, the hyperoxia group (n=42) and the control group (n=42). Oxygen induced retinopathy was established in the hyperoxia group, the control group was raised in room air. Wholemonts were prepared from postnatal day (p) 7 and 14 rat retina to observe retinal vascular morphology. The number of endothelial cells to break through the internal limiting membrane was counted from p14 retinal paraffin sections. Expression of CD147, MMP-2 and VEGF protein levels was analyzed by immunohistochemistry on p12, p14, and p16 retinal sections. At the meantime, correlation between CD147 and MMP-2, VEGF was analyzed by two way analysis of variance (ANOVA) test. Results At p7, the retinal vasculature of the control group was radial distributed with large caliber. In OIR group, there were vasoconstriction, large area of avascular zone and a few small areas of vascular network. At p14, the normal untreated rat had interwoven retinal vasculature, but in OIR group, the retinal vasculature was expanded and tortuous, and forming lots of neovascular cluster in the boundary of the perfusion and non perfusion regions resulting exudation and hemorrhage. At p14, the endothelial cell nuclei breakthrough the internal limiting membrane was (1.30±1.26) and (19.70±3.56) respectively in control and OIR group, the difference was statistically significant (t=21.813, P＜0.01). Immunohistochemical staining showed that CD147, MMP-2, VEGF expression was low in control group but high in OIR group. From p12 to p16, CD147, MMP-2 and VEGF protein expression increased in OIR retinas compared with control samples（p12:t=5.612, 4.122, 4.955; P＜0.01. p14: t=11.390, 8.047, 12.176; P＜0.01. p16: t=6.355, 4.422, 5.110; P＜0.01）. Conclusion CD147, MMP-2 and VEGF were highly expressed in the rat model of oxygen induced retinopathy.