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Myh11R247C杂合突变小鼠胸升主动脉在去甲肾上腺素诱导高血压模型中的病理生理研究

Pathophysiological Study on Thoracic Ascending Aorta of Mice with Myh11R247C Heterozygous Mutation in Norepinephrine-induced Hypertension Model

  • 摘要:
      目的  探索杂合突变Myh11R247C/+小鼠胸升主动脉在去甲肾上腺素诱导高血压模型中的病理生理变化。
      方法  取杂合突变Myh11R247C/+(HET组)和野生型Myh11+/+(WT组)雌鼠,通过腹腔注射去甲肾上腺素诱导高血压模型。利用高频超声和有创动脉血压检测实时采集胸升主动脉直径和颈总动脉有创血压,以此分析两组小鼠胸升主动脉顺应性,并通过组织解剖学比对两组小鼠主动脉夹层破裂发生情况和血胸发生率。
      结果  注射去甲肾上腺素后,HET组胸升主动脉的收缩期扩张百分比和舒张期扩张百分比较WT组分别增加17%和32%(P<0.000 1)。HET组与WT组比较,颈总动脉收缩期或舒张期血压升高百分比的差异无统计学意义。HET组有2例发生了动脉夹层或破裂,且HET组(3/5)相比WT组(0/5)有更高的血胸发生率。
      结论  Myh11R247C/+杂合突变胸升主动脉管壁顺应性的改变可能是其主动脉夹层发生和破裂的重要潜在原因。

     

    Abstract:
      Objevtive  To explore the thoracic ascending aortic (TAA) pathophysiological characteristics of heterozygous mutant Myh11R247C/+ mice under the norepinephrine-induced hypertension mode.
      Methods  Female heterozygous mutant Myh11R247C/+ and wild type Myh11+/+ mice were selected as experimental group (HET group) and control group (WT group), respectively. The hypertensive model was induced by intraperitoneal injection of norepinephrine (NE), and TAA diameter and invasive blood pressure (Bp) data were collected dynamically in real time using high-frequency ultrasound imaging and invasive arterial blood pressure monitoring technique, so as to indirectly analyze TAA compliance of two groups of mice. At the same time, the incidences of hemothorax and TAA rupture were further analyzed by autopsy and histology.
      Results  After injection of NE, heterozygous mice did not show a higher Bp increase percentage in systole or diastole comparing with wildtype mice. However, heterozygous mice exhibited 17% and 32% higher TAA diameter dilation percentage than wildtype ones in systole and diastole respectively. Two heterozygous mice had TAA dissection and rupture, and the incidence of hemothorax in heterozygous mice (3/5) was higher than that in wildtype (0/5).
      Conclusion  It was very likely that the altered TAA wall compliance of mutant Myh11R247C/+ mice had led to a higher TAA dilation degree than that in wildtype, and even could be the potential reason of TAA dissection and rupture.

     

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