2021 年第 3 期 第 16 卷

川芎嗪对冠心病大鼠的血管保护作用研究

Effect of ligustrazine on vascular protection in rats with coronary atherosclerotic heart disease

作者：董小莉马立宁王苗

英文作者：Dong Xiaoli Ma Lining Wang Miao

单位：海南省人民医院海南医学院附属海南医院心血管内科，海口570311

英文单位：Department of Cardiovascular Medicine Hainan Provincial People′s Hospital Hainan Hospital Affiliated of Hainan Medical College Haikou 570311 China

关键词：冠心病（冠状动脉粥样硬化性心脏病）；川芎嗪；血管内皮生长因子信号通路；血管保护

英文关键词：Coronaryatheroscleroticheartdisease;Ligustrazine;Vascularendothelialgrowthfactorsignalingpathway;Vascularprotection

• 摘要：

• 目的 探讨川芎嗪对冠心病（冠状动脉粥样硬化性心脏病）大鼠的血管保护作用。方法 将60只无特定病原体级SD大鼠完全随机分为对照组、模型组和川芎嗪低、中、高剂量组，各12只。除对照组外，其余各组均采用高脂饲料喂养联合腹腔注射维生素D3的 建立冠心病大鼠模型；造模成功后，川芎嗪低、中、高剂量组大鼠分别按照50、100、200 mg/kg腹腔注射20 mg/ml的川芎嗪注射液，对照组及模型组腹腔注射等容积0.9%氯化钠溶液，连续给药4周后，比较各组大鼠体质量增加值、血浆炎症因子、血脂、内皮功能等指标变化，苏木精-伊红染色观察大鼠胸主动脉组织病理学，蛋白质印迹法测定大鼠胸主动脉血管内皮生长因子（VEGF）、VEGF受体2（VEGFR-2）水平。结果 与模型组相比，川芎嗪低、中、高剂量组大鼠体质量增加值，血浆中肿瘤坏死因子α、白细胞介素6及白细胞介素1β水平，血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇水平及动脉粥样硬化指数、血管张力变化值均呈剂量依赖性显著降低（均P＜0.05），血清高密度脂蛋白胆固醇水平呈剂量依赖性显著升高（均P＜0.05）；组织病理学检查结果表明，川芎嗪各剂量组大鼠胸主动脉血管完整性明显改善；川芎嗪各剂量组大鼠胸主动脉血管VEGF、VEGFR-2水平呈剂量依赖性显著升高，川芎嗪低、中、高剂量组VEGF、VEGFR-2均高于模型组［（0.64±0.05）、（0.83±0.02）、（1.02±0.08）μg/L比（0.36±0.04）μg/L，（0.71±0.03）、（0.89±0.05）、（1.18±0.03）μg/L比（0.38±0.02）μg/L］（均P＜0.05）。结论 川芎嗪能够对冠心病大鼠血管起到保护作用，其机制可能与调节VEGF信号通路有关。

• Objective To investigate the protective effect of ligustrazine on vessels in rats with coronary atherosclerotic heart disease (CHD). Methods Sixty SD rats were randomly divided into  control group, model group, low dose ligustrazine group, middle dose ligustrazine group and high dose ligustrazine group, with 12 rats in each group. The rat model of CHD was established by feeding with high fat diet combined with intraperitoneal injection of vitamin D3 in four groups except for the control group. After successful modeling, the rats in the low, middle and high dose groups were intraperitoneally injected with ligustrazine injection 20 mg/ml according to 50, 100 and 200 mg/kg, respectively. The rats in the control group and the model group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution. After 4 weeks of injection, the changes of body weight gain, plasma inflammatory factors, blood lipid and endothelial function were compared among the five groups. The histopathology of thoracic aorta was observed by hematoxylin-eosin staining. The levels of vascular endothelial growth factor(VEGF) and VEGF receptor-2(VEGFR-2) in thoracic aorta were measured by western blotting. Results Compared with the model group, body weight gain, plasma tumor necrosis factor-α, interleukin(IL)-6 and IL-1β levels, serum total cholesterol, triglyceride, low density lipoprotein cholesterol levels and atherosclerotic index, the changes of vascular tension in low, middle and high dose ligustrazine groups significantly decreased in a dose-dependent manner(all P＜0.05), and the level of serum high density lipoprotein cholesterol significantly increased in a dose-dependent manner (all P＜0.05). The histopathological examination showed that the vascular integrity of thoracic aorta was significantly improved in each dose group of ligustrazine, and the levels of VEGF and VEGFR-2 in thoracic aorta were significantly increased in a dose-dependent manner in each dose group of ligustrazine［（0.64±0.05）,（0.83±0.02）,（1.02±0.08）μg/L vs （0.36±0.04）μg/L; （0.71±0.03）,（0.89±0.05）,（1.18±0.03）μg/L vs （0.38±0.02）μg/L］(all P＜0.05). Conclusion Ligustrazine can protect the blood vessels of rats with CHD, and its mechanism may be related to the regulation of VEGF signaling pathway.