羟苯磺酸钙对动脉粥样硬化斑块形成的影响及其机制

目的：探讨羟苯磺酸钙对兔动脉粥样硬化（AS）斑块形成的影响及其作用机制。方法：24只健 康雄性新西兰兔，以液氮冻伤术在兔右颈总动脉处建立AS斑块模型，随机分为模型组和治疗组，每组12只。 模型组给予高脂饲料喂养8周，治疗组给予高脂饲料加羟苯磺酸钙0.15mg·g-1·d -1喂养8周。分别于实验前 及实验8周后取血，ELISA测定血清内皮素-1（ET-1）、一氧化氮（NO）和血管内皮生长因子（VEGF）含量。8周 后处死动物，取右颈总动脉，光镜和电镜观察病理形态学变化，免疫组织化学检测兔右颈总动脉基质金属 蛋白酶9（MMP-9）和纤溶酶原激活物抑制物-1（PAI-1）的表达。结果：8周后，模型组兔血管内膜具有典型 的AS斑块表现，治疗组兔血管内膜AS斑块病变轻微；2组兔颈动脉局部可见PAI-1和MMP-9蛋白表达，但治疗 组的表达量较模型组明显减少，差异有统计学意义（ P ＜0.05）；2组ET-1显著降低，NO、VEGF显著升高，差 异有统计学意义（ P ＜0.05），且治疗组ET-1降低幅度大于模型组，NO、VEGF升高幅度大于模型组，差异有统 计学意义（ P ＜0.05）。结论：羟苯磺酸钙通过减少血管壁局部组织中PAI-1和MMP-9蛋白的表达，降低血循 环中ET-1含量，升高NO、VEGF水平等改善内皮功能障碍，进而发挥抗AS斑块形成作用。

The effect of calcium dobesilate on the formation of atherosclerotic plaques and its mechanism

Objective: To discuss the effect of calcium dobesilate on the formation of atherosclerotic plaques in rabbits and its mechanism. Methods: Atherosclerotic plaque model was set up by liquid nitrogen frostbite in 24 health male New Zealand rabbits. The rabbits were randomly divided as the model group (n=12) and the treatment group (n=12). The model group was given high-fat diet for 8 weeks, while the treatment group was given high-fat diet and calcium dobesilate (0.15 mg·g-1·d-1) for 8 weeks. Serum endothelin-1 (ET-1), nitric oxide (NO) and vascular endothelial growth factor (VEGF) were measured by ELISA before the experiment and after 8 weeks of treatment. After 8 weeks, the animals were killed, the right common carotid artery was removed, and the pathomorphological changes were observed by light microscope and electron microscope. The expression of matrix metalloproteinase 9 (MMP-9) and plasminogen activator inhibitor-1 (PAI-1) were detected by immunohistochemistry. Results: After 8 weeks, the vascular intima in the model group showed typical atherosclerotic plaque lesions, while the vascular intima in the treatment group showed slight atherosclerotic plaque lesions. The expression of PAI-1 and MMP-9 protein was observed locally in the carotid arteries of both groups, but the expression level in the treatment group was significantly lower than that in the model group (P<0.05). The expression of ET-1 was significantly decreased. The expression of NO and VEGF was significantly increased in both groups, but the decrease in ET-1 in the treatment group was greater than that in the model group, the increase in NO and VEGF was greater than that in the model group, with significant difference (P<0.05). Conclusion: Calcium dobesilate can improve endothelial dysfunction by reducing the expression of PAI-1 and MMP-9 proteins in local vascular walls, reducing the ET-1 content in blood circulation and increasing the levels of NO and VEGF, which play the role of anti-atherosclerotic plaque formation.