褐藻糖胶对小鼠颈动脉粥样硬化易损斑块作用及机制  

EFFECT AND MECHANISM OF FUCOIDAN ON CAROTID ATHEROSCLEROTIC VULNERABLE PLAQUES IN MICE

作　　者：程雨菲 朱晓岩[2] 马爱军[1] 潘旭东[1] CHENG Yufei;ZHU Xiaoyan;MA Aijun;PAN Xudong(Department of Neurology,The Affiliated Hospital of the Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院神经内科,山东青岛266003 [2]青岛大学附属医院重症医学科,山东青岛266003

出　　处：《青岛大学学报（医学版）》2020年第5期536-539,共4页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(81571112,81771259)。

摘　　要：目的探讨褐藻糖胶对高脂喂养的ApoE^-/-小鼠颈动脉粥样硬化易损斑块模型的作用及Nod样受体蛋白3(NLRP3)炎症通路蛋白表达的影响。方法雄性ApoE^-/-小鼠36只,随机分为对照组(普通饮食)、模型组(颈动脉套管+高脂饮食+生理盐水)和褐藻糖胶组(颈动脉套管+高脂饮食+褐藻糖胶),每组12只。8周后检测各组小鼠血脂水平,采用苏木精-伊红(HE)染色方法观察小鼠右侧颈总动脉病理改变,ELISA法测定炎性因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子α(TNF-α)表达水平,Western Blot方法检测颈动脉粥样硬化斑块中NLRP3、半胱氨酸天冬氨酸酶-1(Caspase-1)、IL-1β蛋白表达水平。结果与模型组比较,褐藻糖胶组小鼠血脂水平明显降低,颈动脉粥样硬化易损斑块明显减少,IL-1β、IL-6、TNF-α表达降低,差异均有显著性(F=8.31~190.73,P<0.05)。模型组颈动脉粥样硬化斑块中NLRP3、Caspase-1、IL-1β蛋白表达较对照组显著升高,而褐藻糖胶组各蛋白表达较模型组下降(F=50.22~120.59,P<0.05)。结论褐藻糖胶能够通过下调NLRP3炎性小体通路抑制炎症而发挥抗颈动脉粥样硬化作用。Objective To investigate the effect of fucoidan on carotid atherosclerotic vulnerable plaques and expression of Nod-like receptor family,pyrin domain-containing protein 3(NLRP3)-related inflammatory pathway proteins in ApoE^-/- mice fed with high-fat diet.Methods A total of 36 male ApoE^-/- mice were randomly divided into control group(normal diet),model group(carotid collar+high-fat diet+normal saline),and fucoidan group(carotid collar+high-fat diet+fucoidan),with 12 mice in each group.After 8 weeks,blood lipid levels were measured;hematoxylin-eosin staining was used to observe the pathological changes of the right common carotid artery;ELISA was used to measure the levels of the inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α);Western Blot was used to measure the protein expression of NLRP3,Caspase-1,and IL-1βin atherosclerotic plaques.Results Compared with the model group,the fucoidan group had significant reductions in blood lipid levels,carotid atherosclerotic vulnerable plaques,and expression of IL-1β,IL-6,and TNF-α(F=8.31-190.73,P<0.05).Compared with the control group,the model group had significant increases in the protein expression of NLRP3,Caspase-1,and IL-1β in carotid atherosclerotic plaques,and compared with the model group,the fucoidan group had significant reductions in the expression of these proteins(F=50.22-120.59,P<0.05).Conclusion Fucoidan can effectively attenuate carotid atherosclerosis by downregulating the NLRP3 inflammasome pathway.

关 键 词：褐藻糖胶 斑块 动脉粥样硬化 NLR家族 热蛋白结构域包含蛋白3 

分 类 号：R543.5[医药卫生—心血管疾病]