摘要
目的探讨动脉粥样硬化Toll样受体4基因敲除(TLR4-/-)小鼠模型卷曲蛋白(FZD)变化特征及护心康对动脉粥样硬化的干预作用。方法 SPF级TLR4-/-小鼠70只,随机选择12只纳入正常对照组,予以普通饲料喂养;其余58只予以高脂饲料造模,喂养13周后随机选择5只解剖观察胸主动脉,光镜下发现粥样斑块为造模成功。造模成功动物随机分为模型组、护心康组、阿托伐他汀组,Wnt抑制因子(WIF)组,每组12只,分别予以相应处理。处理8周后处死小鼠,心脏穿刺采血检测血脂水平;取胸主动脉,光镜下观察动脉粥样硬化斑块形成情况;免疫组织化学法检测斑块中FZD蛋白的表达。结果模型组胆固醇、三酰甘油、低密度脂蛋白和高密度脂蛋白水平较正常对照组明显升高(P<0.05);阿托伐他汀和护心康可降低胆固醇和低密度脂蛋白水平(P<0.05),WIF对二者的降低作用不明显(P>0.05);3种药物对三酰甘油和高密度脂蛋白的影响相对较小。正常对照组无动脉粥样斑块形成,模型组可见内膜增厚,大量斑块明显形成,血管腔明显减小;各药物干预组斑块病变相对较轻。模型组FZD蛋白表达水平明显高于正常对照组(P<0.05);与模型组相比,3种药物处理组FZD水平均降低(P<0.05),但3种药物处理组FZD水平比较,差异无统计学意义(P>0.05)。结论动脉粥样硬化TLR4-/-小鼠模型胸动脉FZD表达水平明显升高,护心康能降低模型小鼠血脂和FZD表达水平,从而减缓动脉粥样硬化的形成。
Objective To investigate the changes of Frizzled protein(FZD)and the intervention of Huxinkang in Toll like receptor 4 gene knockedout(TLR4^-/-)atherosclerosis mice model.Methods 70 SPF TLR4^-/-mice were fed,among which 12 mice were randomly selected as control group and fed with normal diet.The remaining 58 mice were modeled with high-fat diet.After 13 weeks of feeding,5 mice were randomly selected from modeled mice to observe the thoracic aorta,and atheroma plaque found under light microscopy indicated successful modeling.The successful model animals were randomly divided into model group,Huxinkang group,atorvastatin group and Wnt inhibitor factor(WIF)group,12 in each group,which were treated accordingly.Eight weeks after treatment,the mice were sacrificed and the thoracic aorta was taken.The formation of atheroscle?rosis was observed under light microscope.The expression of FZD proteins in plaques was detected by immunohistochemistry.Results The levels of cholesterol,triglyceride,low-density lipoprotein and high-density lipoprotein in the model group were significantly higher than normal group(P<0.05).Atorvastatin and Huxinkang could reduce cholesterol and low-density lipopro?tein levels(P<0.05),and WIF had no significant effect on the reduction of the two indicators.The effects of three drugs on tri-glyceride and high-density lipoprotein were relatively small.No plaques were formed in mice of control group.A large number of plaques were formed in the model group,and the intima thickened,so the vascular lumen was significantly reduced,but the plaque lesions in each drug intervention group were relatively light.The expression of FZD protein in the model group was significantly higher than control group(P<0.05).Compared with model group,expression levels of FZD in the all three drugs treated groups were lower(P<0.05),but there was no significant difference between the three drugs treated groups(P>0.05).Conclusion The expression of FZD could be significantly increased in TLR4^-/-mice with atherosclerosis.Huxinkan
作者
董晓斐
丁小玉
贺佳幸
屈波
DONG Xiaofei;DING Xiaoyu;HE Jiaxing;QU Bo(Department of Pediatrics,the First Affiliated Hospital of Hu′nan University of Traditional Chinese Medicine,Changsha,Hu′nan 410007,China;the Department of Histology and Embryology,the Medical College of Hunan University of Tradition.al Chinese Medicine,Changsha,Hunan 410208,China)
出处
《现代医药卫生》
2018年第24期3749-3752,共4页
Journal of Modern Medicine & Health
基金
国家自然科学基金项目(81473615)
湖南省科技厅自然基金项目(2015JJ2017)
