摘要
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0.15 mg·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。
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.
作者
王莹
李彩
朱峰
金笑平
WANG Ying;LI Cai;ZHU Feng;JIN Xiaoping(Department of Neurology,Taizhou Hospital,Taizhou 317000,China)
出处
《温州医科大学学报》
CAS
2020年第5期387-390,共4页
Journal of Wenzhou Medical University
基金
浙江省公益技术应用社会发展项目(LGF18H090019)。
