黄芪甲苷抑制苯并芘相关性腹主动脉瘤形成的机制研究
Mechanisms of astragaloside inhibiting benzopyrene related abdominal aortic aneurysm formation
蒋凤春 1隋向前 1王文婷 1谢明斌 1姚强 1黄琪1
作者信息
- 1. 310003 杭州,浙江省中西医结合医院心内科
- 折叠
摘要
目的 研究黄芪甲苷(AS-Ⅳ)对苯并芘诱导的小鼠腹主动脉瘤(AAA)形成的抑制作用及机制.方法 32只C57/B6小鼠随机分为对照组、模型组、低剂量AS-Ⅳ组、高剂量AS-Ⅳ组.除对照组外,其余3组小鼠均皮下注射血管紧张素Ⅱ、腹腔注射苯并芘建立AAA模型,低剂量AS-Ⅳ组和高剂量AS-Ⅳ组分别予AS-Ⅳ 20、80 mg/(kg·d)灌胃处理.4周后取各组小鼠腹主动脉观察大体标本形态,HE染色观察血管结构,检测总胆固醇(TC)、甘油三酯(TG)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平,免疫组化法检测靶血管基质金属蛋白酶-2(MMP-2)的表达.结果 对照组、模型组、低剂量AS-Ⅳ组及高剂量AS-Ⅳ组的腹主动脉血管周长明显大于对照组(P＜0.001),模型组＞高剂量AS-Ⅳ组(P＜0.05).HE染色显示动脉瘤形成处弹性纤维紊乱、血管壁变薄.与对照组比较,模型组小鼠血清TC、TG、TNF-α、IL-6水平明显升高(均P＜0.01);与模型组比较,低剂量AS-Ⅳ组及高剂量AS-Ⅳ组上述指标水平均下降(均P＜0.05).与模型组比较,高剂量AS-Ⅳ组MMP-2水平明显下降(P＜0.01).结论 AS-Ⅳ对苯并芘诱导的小鼠AAA形成有抑制作用,可能与降低血管壁MMP-2表达有关.
Abstract
Objective To explore the inhibitory effect of astragaloside Ⅳ(AS-Ⅳ)on the formation of abdominal aortic aneurysm(AAA)induced by benzopyrene in mice and its mechanisms.Methods Thirty-two C57/B6 mice were randomly divided into a control group,model group,low-dose AS-Ⅳ group and high-dose AS-Ⅳ group.Except the control group,mice in other 3 groups were injected subcutaneously with angiotensin Ⅱ and intraperitoneally with benzopyrene to establish AAA model.The low-dose AS-Ⅳ group and high-dose AS-Ⅳ group were fed AS-Ⅳ 20 and 80 mg/(kg·d)by gavage,respectively.Four weeks later,the abdominal aorta of mice in each group was taken to observe the morphology of gross specimens,observe the vascular structure with HE staining.Total cholesterol(TC),triglyceride(TG),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected.The expression of target vascular matrix metalloproteinase-2(MMP-2)was detected by immunohistochemistry.Results The abdominal aortic circumference was significantly larger in the model group,low-dose and high-dose AS-Ⅳ groups than in the control group(P＜0.001),and was significantly larger in the model group than in the high-dose AS-Ⅳ group(P＜0.05).HE staining showed disarranged elastic fibers and vessel wall thinning at the site of aneurysm formation.Compared with the control group,the contents of TC,TG,TNF-α and IL-6 in serum of mice in the model group were significantly increased(all P＜0.01).Compared with the model group,serum above indexes of the low-dose AS-Ⅳ group and high-dose AS-Ⅳ group were decreased(all P＜0.05).Compared with the model group,MMP-2 decreased significantly in the high-dose AS-Ⅳ group(P＜0.01).Conclusion AS-Ⅳ has inhibit effect on mice AAA induced by benzopyrene,which may be related to decreased expression of MMP-2 in vascular wall.
关键词
腹主动脉瘤/黄芪甲苷/血脂/炎症/基质金属蛋白酶-2Key words
Abdominal aortic aneurysm/Astragaloside/Blood lipids/Inflammation/Matrix metalloproteinase-2引用本文复制引用
基金项目
浙江省中医药局科技项目(2023ZL553)
出版年
2024
NETL
NSTL
万方数据