Three paradigms of airway smooth muscle hyperresponsiveness in young guinea pigs.
Three paradigms of airway smooth muscle hyperresponsiveness in young guinea pigs.
复制标题
幼年豚鼠气道平滑肌高反应性的三种范例。
DOI：
10.1139/y07-063
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发表时间：
2007
影响因子：
2.1
通讯作者：
Murphy,ThomasM
中科院分区：
文献类型：
--
作者：
Chitano,Pasquale;Wang,Lu;Murphy,ThomasM
气道平滑肌（ASM）对新生儿和青少年气道高反应性的贡献的证据不断积累。在我们的实验室中，新生儿和年轻的ASM的高反应性的3个新的范例最近出现了使用豚鼠模型的成熟在3个年龄组：1周（新生儿），3周（少年），和2-3个月（成人）。第一个范例包括新生儿和青少年生命后ASM缩短速度的自然下降与调节肌球蛋白轻链磷酸化的减少和肌球蛋白轻链激酶含量的平行下降相关的证据。随着年龄的增长，ASM缩短的减少与缩短的内部阻力增加有关。动态刚度与肌球蛋白轻链激酶的表达呈负相关。这表明，缩短的发育变化与ASM早期缩短的刚度成反比，表明细胞骨架在促进和反对ASM缩短中的动态作用。该关系可以近似为（dP/dt）max ×（dP/dL）passive×（dL/dt）max（主动应力产生的最大增加速率×被动刚度×最大缩短速度）。第二个范例表明，新生儿ASM，不像在成人中，不放松，在长时间的电场刺激。松弛受损与前列腺素合成和乙酰胆碱酯酶功能的变化有关。第三范式表明，而振荡应变短暂放松成人ASM，在新生儿中，它诱导（初始放松后）持续增强主动应力。这与前列腺素释放的发育变化有关。总之，这些范例表明ASM通过多种机制促成新生儿和青少年气道的天然高反应性。未来的研究将详细阐述这些机制，并将这些范例扩展到早期生活中致敏后的ASM高反应性。
Evidence for contributions of airway smooth muscle (ASM) to the hyperresponsiveness of newborn and juvenile airways continues to accumulate. In our laboratory, 3 novel paradigms of hyperresponsiveness of newborn and young ASM have recently emerged using a guinea pig model of maturation in 3 age groups: 1 week (newborn), 3 weeks (juvenile), and 2–3 months (adult). The first paradigm includes evidence for a natural decline after newborn and juvenile life of the velocity of ASM shortening associated with a decrease in regulatory myosin light chain phosphorylation and a parallel decline in the content of myosin light chain kinase. Associated with the decrease in ASM shortening with age is an increase in the internal resistance to shortening. Dynamic stiffness is shown to relate inversely to the expression of myosin light chain kinase. This suggests that developmental changes in shortening relate inversely to the stiffness of the ASM early in shortening, suggesting a dynamic role for the cytoskeleton in facilitating and opposing ASM shortening. This relationship can be approximated as (dP/dt)max≈ (dP/dL)passive× (dL/dt)max(the maximal rate of increase of active stress generation ≈ to the passive stiffness × the maximal shortening velocity). The second paradigm demonstrates that newborn ASM, unlike that in adults, does not relax during prolonged electric field stimulation. The impaired relaxation is related to changes in prostanoid synthesis and acetylcholinesterase function. The third paradigm demonstrates that, whereas oscillatory strain serves to transiently relax adult ASM, in newborns it induces (after the initial relaxation) a sustained potentiation of active stress. This is related to developmental changes in the prostanoid release. Together, these paradigms demonstrate that ASM contributes by multiple mechanisms to the natural hyperresponsiveness of newborn and juvenile airways. Future studies will elaborate the mechanisms and extend these paradigms to ASM hyperresponsiveness following sensitization in early life.