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目的观察多沙唑嗪及美托洛尔对腹主动脉缩窄(AAC)诱导的大鼠血管重塑的影响。方法采用AAC法成功建立血管重塑大鼠模型。2周后每天ig给予多沙唑嗪10 mg·kg-1或美托洛尔20 mg·kg-1,连续6周。采用颈总动脉插管测量大鼠的平均动脉压;采用HE染色和图像分析仪检测大鼠主动脉中膜厚度、中膜面积和中膜厚度与管腔内径比值;Masson染色检测纤维化;Western蛋白印迹法检测胶原蛋白和纤连蛋白表达。结果与假手术组血压(17.6±0.5)k Pa相比,模型组大鼠血压(23.3±0.7)k Pa显著升高(P<0.05),给予多沙唑嗪〔(20.5±0.7)k Pa〕或美托洛尔〔(19.0±0.4)k Pa〕均可有效降低血压(P<0.05)。HE染色结合图像分析仪分析发现,模型组大鼠血管中膜厚度、中膜面积及中膜厚度与血管内径比值较假手术组分别升高39.5%,46.4%和27.0%(P<0.05),给予多沙唑嗪或美托洛尔使血管的中膜厚度分别下降16.0%和26.1%(P<0.05),中膜面积分别下降22.8%和29.1%(P<0.05),中膜厚度与血管内径比值分别下降17.0%和26.0%(P<0.05)。Masson染色结果显示,与假手术组相比,模型组大鼠血管组织胶原蛋白的沉积增多,血管出现纤维化;而给予多沙唑嗪或美托洛尔可以缓解高血压诱导的纤维化发生。Western蛋白印迹结果显示,模型组大鼠血管组织中胶原蛋白和纤连蛋白的表达明显增加(P<0.05),而多沙唑嗪组和美托洛尔组较模型组胶原蛋白和纤连蛋白表达显著下降(P<0.05)。结论多沙唑嗪和美托洛尔可能通过抑制去甲肾上腺素与其特异性受体结合,从而选择性地阻断去甲肾上腺素对血管的诱导作用,逆转高血压诱导的血管重塑的发生。
Objective To observe the effect of doxazosin and metoprolol on vascular remodeling induced by abdominal aorta constriction (AAC) in rats. Methods AAC was used to establish a rat model of vascular remodeling. After 2 weeks, doxazosin 10 mg · kg-1 or metoprolol 20 mg · kg-1 was administered daily for 6 weeks. The mean arterial pressure of the rats was measured by intubation of the common carotid artery. The aortic media thickness, the area of the media and the ratio of the media thickness to the lumen of the lumen were detected by HE staining and image analyzer. The fibrosis was detected by Masson staining. Western blotting was used to detect the expression of collagen and fibronectin. Results The blood pressure (23.3 ± 0.7) kPa in model group was significantly higher than that in sham operation group (17.6 ± 0.5) kPa (P <0.05), and the dose of doxazosin 〔(20.5 ± 0.7) kPa 〕 Or metoprolol (19.0 ± 0.4 kPa〕 〔〕 can be effective in lowering blood pressure (P <0.05). The results of HE staining and image analyzer showed that the ratio of medial thickness, medial area, medial thickness and vascular diameter in model group were increased by 39.5%, 46.4% and 27.0% respectively compared with those in sham operation group (P <0.05) Administration of doxazosin or metoprolol decreased the media thickness by 16.0% and 26.1% (P <0.05), while the media area decreased by 22.8% and 29.1%, respectively (P <0.05) The inner diameter ratio decreased by 17.0% and 26.0% respectively (P <0.05). The results of Masson staining showed that compared with the sham-operation group, collagen deposition in the vascular tissue of the model group increased and fibrosis of the blood vessel appeared. The administration of doxazosin or metoprolol could alleviate the hypertension-induced fibrosis. Western blot results showed that the expression of collagen and fibronectin in the model group was significantly increased (P <0.05), while the expression of collagen and fibronectin in the doxazosin group and metoprolol group was higher than that in the model group Significantly decreased (P <0.05). Conclusion Doxazosin and metoprolol may selectively block the induction of norepinephrine on blood vessels and reverse the occurrence of hypertension-induced vascular remodeling by inhibiting the binding of norepinephrine to its specific receptors.