冠心宁片减轻大鼠颈动脉粥样硬化斑块损伤

doi:10.16352/j.issn.1001-6325.2024.02.0192

摘要/Abstract

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。

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

Abstract: 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) and β-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, hs-CRP, ox-LDL, MDA levels, MMP-9, Wnt3a, β-catenin protein expression, and total plaque area/total arterial area ratio in the high dose+LiCl group of Guanxinning tablets increased, the HDL level decreased(P＜0.05). Conclusions Guanxinning tablet can inhibit the formation of atherosclerotic plaque in rats and the mechanismis potentially related to the regulation of Wnt/β-catenin pathway.

Key words: Guanxinning tablets, Wnt/β-catenin pathway, atherosclerosis, plaque, oxidative stress

中图分类号:

R965

张秀丽, 胡孝刚, 莫俊, 陈铃. 冠心宁片减轻大鼠颈动脉粥样硬化斑块损伤[J]. 基础医学与临床, 2024, 44(2): 192-198.

ZHANG Xiuli, HU Xiaogang, MO Jun, CHEN Ling. Guanxinning tablet alleviates carotid atherosclerotic plaque injury in rats[J]. Basic & Clinical Medicine, 2024, 44(2): 192-198.

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