冠心宁片减轻大鼠颈动脉粥样硬化斑块损伤  

Guanxinning tablet alleviates carotid atherosclerotic plaque injury in rats

作　　者：张秀丽 胡孝刚 莫俊 陈铃 ZHANG Xiuli;HU Xiaogang;MO Jun;CHEN Ling(Department of Geriatric Respiratory and Critical Care Medicine,the Second People′s Hospital of Lishui,Lishui 323000,China;Department of Geriatric Psychiatry,the Second People′s Hospital of Lishui,Lishui 323000,China)

机构地区：[1]丽水市第二人民医院老年呼吸及重症医学科,浙江丽水323000 [2]丽水市第二人民医院老年精神科,浙江丽水323000

出　　处：《基础医学与临床》2024年第2期192-198,共7页Basic and Clinical Medicine

基　　金：浙江省医学会临床科研资金(2019ZYC-A72)。

摘　　要：目的 探讨冠心宁片对大鼠颈动脉粥样硬化斑块的作用机制。方法 将大鼠随机分为对照组、模型组(构建颈动脉粥样硬化斑块模型)、冠心宁片低、中和高剂量组(150、300和600 mg/kg)、阿托伐他汀组(2 mg/kg)、氯化锂[LiCl, Wnt/β-连环蛋白(β-catenin)通路激活剂]组(15 mg/kg)、冠心宁片高剂量+LiCl组(600 mg/kg冠心宁片+15 mg/kg LiCl),每组12只。第3周开始干预,给药1次/d,持续8周。利用Olympus Au2700全自动生化分析仪检测大鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)含量;ELISA检测大鼠血清中单核细胞趋化蛋白(MCP-1)、超敏C反应蛋白(hs-CRP)含量;分光光度法检测大鼠血清中氧化型低密度脂蛋白(ox-LDL)、丙二醛(MDA)含量;HE染色检测大鼠颈总动脉病理变化;Western blot检测大鼠颈总动脉中Wnt3a、基质金属蛋白酶-9(MMP-9)、β-catenin蛋白。结果 与对照组比较,模型组TG、TC、LDL、MCP-1、hs-CRP、ox-LDL、MDA含量、MMP-9、Wnt3a、β-catenin蛋白表达及斑块总面积/动脉总面积升高,HDL含量降低(P<0.05);与模型组比较,冠心宁片低、中、高剂量组、阿托伐他汀组TG、TC、LDL、MCP-1、hs-CRP、ox-LDL、MDA含量、MMP-9、Wnt3a、β-catenin蛋白表达及斑块总面积/动脉总面积降低,HDL含量升高,且冠心宁片呈剂量依赖性,LiCl组对应指标变化趋势与上述相反(P<0.05);与冠心宁片高剂量组比较,冠心宁片高剂量+LiCl组TG、TC、LDL、MCP-1、hs-CRP、ox-LDL、MDA含量、MMP-9、Wnt3a、β-catenin蛋白表达及斑块总面积/动脉总面积升高,HDL含量降低(P<0.05)。结论 冠心宁片具有抑制大鼠动脉粥样硬化斑块形成的作用,其机制可能与调控Wnt/β-catenin通路有关。Objective To investigate the effect and its mechanism of Guanxinning tablet on carotid atherosclerotic plaque in a rat model.Methods The rats were randomly divided into control group,model group(to construct carotid atherosclerosis plaque model),Guanxinning groups with low,medium and high dose of Guanxinning tablet(150,300 and 600 mg/kg),atorvastatin group(2 mg/kg),lithiumchloridemonohydrate(LiCl)(Wnt/β-catenin pathway activator)group(15 mg/kg),and Guanxinning plus LiCl group(600 mg/kg Guanxinning tablets+15 mg/kg LiCl),with 12 rats in each group.The intervention began at the third week and was administered once a day for 8 weeks.Olympus Au2700 automatic biochemical analyzer was used to detect the level of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL)and high-density lipoprotein(HDL)in rat serum;ELISA was applied to detect the level of monocyte chemotactic protein(MCP-1)and hyper-sensitive C-reactive protein(hs-CRP)in rat serum;the level of oxidized low density lipoprotein(ox-LDL)and malondialdehyde(MDA)in rat serum were detected by spectrophotometry;HE staining was applied to find pathological changes in the common carotid artery of rats;Western blot was applied to detect the expression of Wnt3a,matrix metalloproteinase-9(MMP-9)andβ-catenin in rat common carotid artery.Results Compared with the control group,the level of TG,TC,LDL,MCP-1,hs-CRP,ox-LDL,protein expression of MDA,MMP-9,Wnt3a,β-catenin and total plaque area/total arterial area ratio increased,the HDL level decreased in model group(P<0.05);compared with the model group,the level of TG,TC,LDL,MCP-1,hs-CRP,ox-LDL,MDA,expression of MMP-9,Wnt3a,β-catenin protein and total plaque area/total arterial area ratio in the low,medium,and high dose groups of Guanxinning tablets decreased,the HDL level increased.The effect of Guanxinning tablets was dose-dependent,and the change trend of corresponding indicators in the LiCl group was opposite to the above(P<0.05);compared with the high dose group of Guanxinning tablets,the TG,TC,LDL,MCP-1

关 键 词：冠心宁片 Wnt/β-连环蛋白通路 动脉粥样硬化 斑块 氧化应激 

分 类 号：R965[医药卫生—药理学]