刘巨鹏,李建权.酒石酸美托洛尔调节TGF-β/Smad信号通路抑制大鼠胸主动脉瘤进程的机制研究[J].药物评价研究,2019,42(5):840-845
酒石酸美托洛尔调节TGF-β/Smad信号通路抑制大鼠胸主动脉瘤进程的机制研究
Metoprolol tartrate suppressed thoracic aortic aneurysms progression of rats by regulating TGF-β/Smad signal pathway
投稿时间:2018-08-28  
DOI:10.7501/j.issn.1674-6376.2019.05.006
中文关键词:  酒石酸美托洛尔;TGF-β/Smad信号通路;胸主动脉瘤
英文关键词:metoprolol tartrate;TGF-β/Smad signal pathway;thoracic aortic aneurysms
基金项目:
作者单位E-mail
刘巨鹏 包钢集团第三职工医院, 内蒙古 包头 014010  
李建权 包钢集团第三职工医院, 内蒙古 包头 014010 jupeng123666@126.com 
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中文摘要:
      目的 研究酒石酸美托洛尔通过调节转化生长因子-β(TGF-β)/Smad信号通路抑制大鼠胸主动脉瘤(TAA)进程的分子机制。方法 暴露大鼠胸降主动脉1 cm,将已用0.5 mol/L的氯化钙浸泡好的棉纱覆盖血管外膜15~20 min,建立TAA模型,设置模型组和酒石酸美托洛尔高、中、低剂量(0.60、0.30、0.15 mg/kg)组,另取10只大鼠作为对照组,每天1次,连续ig给药4周,模型组和对照组ig等体积蒸馏水。对大鼠生理活动进行观察和记录,HE染色观察动脉管腔面改变;实时荧光定量PCR (qRT-PCR)和Western blotting对大鼠TAA组织中的TGF-β、Smad2、Smad3的表达水平进行检测。结果 与对照组比较,模型组大鼠进食较少,体质量减轻,精神萎靡,毛发杂乱,无光泽,活动减少;酒石酸美托洛尔组与模型组比较,生理状态好转;HE染色显示,对照组主动脉壁弹力板排列规则、紧密,呈波浪形膜状;模型组动脉瘤壁的弹力板平直,并且有断裂现象;与模型组比较,酒石酸美托洛尔组弹力板断裂减少,动脉壁呈波浪形膜状。与对照组比较,模型组瘤组织中的TGF-β、Smad2、Smad3的mRNA、蛋白表达水平均显著上调(P<0.05);与模型组织比较,酒石酸美托洛尔组TGF-β、Smad2、Smad3的mRNA、蛋白表达水平均显著下调(P<0.05),且呈剂量相关性。结论 酒石酸美托洛尔通过调节TGF-β/Smad信号通路抑制大鼠TAA的进程。
英文摘要:
      Objective To investigate metoprolol tartrate regulated TGF-β/Smad signal pathway suppressed thoracic aortic aneurysms progression. Methods After exposing the descending thoracic aorta of rats for 1 cm, the cotton yarn immersed in 0.5 mol/L calcium chloride was covered with adventitia for 15~20 minutes to establish TAA model. The model group, the high, medium and low dose of metoprolol tartrate (0.60, 0.30, 0.15 mg/kg) group were set up, another 10 rats were taken as control group. Corresponding drugs was ig administered once a day for four weeks, distilled water was ig administered in model group and control group. The physiological activities of rats were observed and recorded, HE staining was used to observe the changes of arterial lumen surface. TGF-β, Smad2, Smad3 mRNA detected by real time PCR, and TGF-β, Smad2, Smad3 protein level analyzed by western blotting. Results Compared with control group, rats in model group ate less, had lighter body weight, mental retardation, disordered hair, no luster and less activity; compared with model group, the physiological state of the rats in the metoprolol tartrate group improved. HE staining showed that the elastic plates in the aortic wall of the control group were arranged regularly and tightly in a wavy membrane shape; the elastic plates in the aneurysm wall of the model group were straight and fractured; compared with the model group, the elastic plates in the metoprolol tartrate group were less fractured and the arterial wall was wavy membrane shape. Compared with the control group, the expression levels of TGF-β, Smad2 and Smad3 in model group were significantly increased (P<0.05); compared with model group, the expression levels of TGF-β, Smad2 and Smad3 in the metoprolol tartrate group were significantly decreased (P<0.05), and there was a dose-dependent relationship. Conclusion metoprolol regulated TGF-β/Smad signal pathway suppressed thoracic aortic aneurysms progression.
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