松果菊苷对动脉粥样硬化血管钙化小鼠Wnt/β-连环蛋白信号通路的影响  

Effects of echinoside on Wnt/β-catenin signaling pathway in atherosclerotic vascular calcification mice

作　　者：袁媛 贾哲睿 王晨皓 刘涛[2] 赵军 何丽娟[2] 陶宁[2] 由淑萍[1] YUAN Yuan;JIA Zherui;WANG Chenhao;LIU Tao;ZHAO Jun;HE Lijuan;TAO Ning;YOU Shuping(School of Nursing,Xinjiang Medical University,Urumqi 830011,China;不详)

机构地区：[1]新疆医科大学护理学院,乌鲁木齐830011 [2]新疆医科大学公共卫生学院,乌鲁木齐830011 [3]新疆维吾尔自治区药物研究所

出　　处：《浙江医学》2024年第6期588-593,598,共7页Zhejiang Medical Journal

基　　金：新疆维吾尔自治区省部共建中亚高发病成因与防治国家重点实验室开放课题(SKL-HIDCA-2021-28);新疆医科大学(国家级)大学生创新训练计划项目(202210760016)。

摘　　要：目的探究松果菊苷对动脉粥样硬化血管钙化小鼠Wnt/β-catenin信号通路的影响。方法将48只7周龄雄性ApoE-/-小鼠采用随机数字表法分为6组,每组8只:分别为模型组,松果菊苷(ECH)12.5、25、50 mg/kg组,辛伐他汀片(Sta)组和对照组,依据不同分组建模及给药。观察小鼠主动脉组织形态学变化,检测小鼠血清中生化指标水平,采用实时荧光定量PCR法检测小鼠主动脉组织β-连环蛋白(β-catenin)mRNA的表达水平,采用Western Blot法检测小鼠主动脉组织β-catenin、Wnt3a、LDL受体相关蛋白5(LRP5)及骨形态发生蛋白2(BMP-2)蛋白表达水平,采用免疫组化法检测小鼠主动脉组织LRP5蛋白表达水平。结果ECH 25、50 mg/kg组及Sta组小鼠主动脉中膜较模型组明显变薄,弹力纤维排列整齐,斑块明显缩小。ECH 25、50 mg/kg组和Sta组TG、TC、LDL-C水平均低于模型组,差异均有统计学意义(均P<0.01)。ECH 12.5、25、50 mg/kg组和Sta组HDL-C水平均高于模型组,差异均有统计学意义(均P<0.01)。模型组小鼠主动脉β-cateninmRNA表达水平高于对照组,ECH 12.5、25、50 mg/kg组及Sta组β-cateninmRNA表达水平均低于模型组,差异均有统计学意义(均P<0.05)。模型组小鼠模型组小鼠主动脉β-catenin、Wnt3a、LRP5及BMP-2蛋白表达水平高于对照组,ECH 25、50 mg/kg组及Sta组小鼠主动脉β-catenin、Wnt3a、LRP5及BMP-2蛋白表达水平均低于模型组,差异均有统计学意义(均P<0.05)。模型组小鼠主动脉LRP5蛋白表达水平高于对照组,差异有统计学意义(P<0.05)。ECH 12.5、25、50 mg/kg组及Sta组LRP5蛋白表达水平均低于模型组,差异均有统计学意义(均P<0.01)。结论ECH可以有效改善小鼠动脉粥样硬化血管钙化的发生与发展,其机制可能与调控Wnt/β-catenin信号通路相关。Objective To investigate the effect of echinoside(ECH)on the Wnt/β-catenin signaling pathway in mice with atherosclerotic(AS)vascular calcification.Methods Forty-eight 7-week-old male ApoE-/-mice were randomly divided into 6 groups,each with 8 mice:model group,ECH 12.5,25 and 50 mg/kg groups,Sta group,and control group,and they were given different treatment regimens.HE staining was used to observe the tissue ecological changes in the aorta of mice,and to detect the levels of biochemical indexes in the serum of mice.The expression level of aorticβ-catenin mRNA was detected by RT-qPCR,the expression levels of aorticβ-catenin,Wnt3a,LRP5 and BMP 2 were detected by Western blotting,and the expression level of aortic LRP5 was detected by immunohistochemistry.Results The mem branes in the ECH 25,ECH 50 mg/kg and Sta groups were significantly thinner than those of the model group,with aligned elastic fibres and significantly reduced plaques;while the levels of serum TG,TC,and LDL-C in the three groups were statistically lower compared with the control group(all P<0.01).HDL-C level in the ECH 12.5,25 and 50 mg/kg groups and Sta group was significantly higher than that of the model group(all P<0.001).In the model group,aorticβ-catenin mRNA expression level was higher than that of the control group,whileβ-catenin mRNA expression level in the ECH 12.5,25,and 50 mg/kg groups and the Sta group was lower than that of the model group,differences of which were all statistically significant(all P<0.05).The protein expression levels of aorticβ-catenin,Wnt3a,LRP5 and BMP-2 in the model group were higher than those of the control group,as well as ECH 25 and 50 mg/kg groups and Sta group,and the differences were statistically significant(all P<0.01).In the model group,aortic LRP5 protein expression level was statistically higher than that of the control group(P<0.05),as well as ECH 12.5,25,and 50 mg/kg groups and the Sta group(all P<0.01).Conclusion ECH effectively ameliorates the onset and development of AS calcification of Ap

关 键 词：松果菊苷 Wnt/β-连环蛋白信号通路 APOE-/-小鼠 动脉粥样硬化 血管钙化 

分 类 号：R285.5[医药卫生—中药学]