Changes in murine anorectum signaling across the life course.

Changes in murine anorectum signaling across the life course.
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DOI:
10.1111/nmo.13426
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发表时间:
2018-10
影响因子:
3.5
通讯作者:
Yeoman MS
Yeoman MS
中科院分区:
医学3区
文献类型:
--
作者:
Fidalgo S;Patel BA;Ranson RN;Saffrey MJ;Yeoman MS

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年龄的增加与慢性便秘和粪便嵌塞的发生率增加有关。自然老化过程对这些条件的贡献尚未完全了解。本研究探讨了年龄增长对小鼠肛门直肠功能的影响。使用经典的器官浴试验检查年龄增加对小鼠肛门直肠中胆碱能、氮能和嘌呤能信号通路的影响,以检查组织功能和电化学传感,以确定一氧化氮和乙酰胆碱释放的年龄相关变化。氮能松弛在3至6个月之间增加,在12个月达到峰值,在18和24个月组下降。这些变化的部分原因是年龄相关的一氧化氮(NO)释放减少。胆碱能信号保持随着年龄的增加,乙酰胆碱(ACh)的释放和胆碱酯酶活性的代偿性下降。年龄相关的嘌呤能松弛变化在性质上与氮能松弛相似,尽管松弛要小得多。增加年龄并没有改变肛门直肠平滑肌的反应,外源性应用乙酰胆碱,ATP,硝普钠或氯化钾。同样,肛门直肠的基础张力也没有变化。随着年龄的增长,氮能信号传导的减少可能通过部分阻碍排便而导致先前在该模型中描述的年龄相关的粪便嵌塞和便秘。
Increasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum. The effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age‐related changes in nitric oxide and acetylcholine release. Nitrergic relaxation increased between 3 and 6 months, peaked at 12 months and declined in the 18 and 24 months groups. These changes were in part explained by an age‐related decrease in nitric oxide (NO) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (ACh) release and a compensatory decrease in cholinesterase activity. Age‐related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied ACh, ATP, sodium nitroprusside or KCl. Similarly, there was no change in basal tension developed by the anorectum. The decrease in nitrergic signaling with increasing age may contribute to the age‐related fecal impaction and constipation previously described in this model by partially obstructing defecation.
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