螺内酯对碱烧伤诱导大鼠角膜新生血管形成的影响及其机制研究

背景：螺内酯为醛固酮受体拮抗剂，近来有实验证实螺内酯在体内外能够有效地抑制新生血管的形成。目的：验证螺内酯对碱烧伤诱导大鼠角膜新生血管的抑制作用。方法：取SD大鼠36只，采用碱烧伤方法制备大鼠角膜新生血管模型，造模后以数字表法随机分成实验组和对照组。实验组术后灌胃给予螺内酯100 mg/kg，1次/d，对照组灌胃给予等量生理盐水。另取大鼠6只不作任何处理作为正常对照组。于造模后4，7，14 d运用裂隙灯观察各组大鼠角膜新生血管并计算面积，并每组随机处死6只大鼠，运用免疫组化染色方法和计算机图像分析系统检测观察血管内皮细胞生长因子及基质金属蛋白酶2的表达。结果与结论：正常角膜组织未见炎症细胞与新生血管，角膜上皮及基质层仅见微弱血管内皮细胞生长因子表达，未见基质金属蛋白酶2表达。与对照组比较，实验组各个时期新生血管面积减小，血管内皮细胞生长因子和基质金属蛋白酶2表达降低(P < 0.05)。提示螺内酯可能通过参与下调血管内皮生长因子和基质金属蛋白酶2表达，从而有效地抑制角膜新生血管的形成。

Eftects and mechanisms of spironolactone on corneal neovascularization after corneal alkali burn in rats

BACKGROUND: Spironolactone is an aldosterone antagonist, which was confirmed to possess inhibition effect on the angiogenesis in vitro and in vivo.OBJECTIVE: To verify the effect of spironolactone on corneal neovascularization (CRNV) of the rats induced by alkali burns.METHODS: Corneal models induced by alkali burn were established on 36 SD rats, which were random divided into the experimental group (treated orally with SL 100mg/kg once a day) and control group (treated with the same volume of normal saline). Additional 6 rats were served as normal control group without treatment. The length and area of CRNV in each group were examined by microscope at days 4, 7 and 14 after operation. Six rats of each group were killed and the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in cornea were detected with immunohistochemistry and computer image analysis system.RESULTS AND CONCLUSION: Corneal neovascularization and inflammatory cells were not be found in the normal corneal, and there was a little expression of VEGF in the normal corneal epithelium and stroma but not detected the expression of MMP-2. Compared with control group, the area of blood vessels was significant smaller and the expression of VEGF and MMP-2 were significant lower (P < 0.05) at different observing times. Spironolactone can inhibit the occurrence of CRNV by down regulating the expression of VEGF and MMP-2.