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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
【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-Ⅳ20、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 and80 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.
【Key words】 Abdominal aortic aneurysm; Astragaloside; Blood lipids; Inflammation; Matrix metalloproteinase-2;
- 【文献出处】 心电与循环 ,Journal of Electrocardiology and Circulation , 编辑部邮箱 ,2024年03期
- 【分类号】R285.5
- 【下载频次】24