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舍曲林和去甲替林能否保护大鼠结肠黏膜下和肌间神经丛中的神经元免受应激损伤?

Can Sertraline and Nortriptyline Protect the Neurons in Submucosal and Myenteric Plexuses of Rat's Colon Against Stress?

机构信息

Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Zand Ave., Shiraz, 71348-45794, Iran.

Anatomy Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Dig Dis Sci. 2019 Sep;64(9):2548-2554. doi: 10.1007/s10620-019-05600-y. Epub 2019 Apr 1.

Abstract

BACKGROUND

The colon is partly controlled by myenteric and submucosal plexuses, which respond to stress and lead to some gastrointestinal disorders. These plexuses play roles in irritable bowel syndrome. Patients suffering from this syndrome can be treated with some antidepressants, including sertraline and nortriptyline.

AIMS

The primary aim of study was to compare the effect of a sertraline and a nortriptyline on the structural changes of the enteric neurons after stress exposure in both sexes. The secondary objectives were to evaluate the effects of stress on the submucosal and myenteric plexuses.

METHODS

Male and female Sprague-Dawley rats were assigned to four subgroups. The first subgroup received no stress. The other three subgroups received chronic variable stress (CVS) and were given phosphate buffer, sertraline (10 mg/kg/day), or nortriptyline (10 mg/kg/day). After 45 days, the neuron number in their colon plexuses was estimated using the stereologic method.

RESULTS

The number of neurons increased by 40-51% in the submucosal plexus and by 57-69% in the myenteric plexus in the CVS group compared with the control group (p < 0.002) without any sex preference. The increment was significantly higher in the myenteric plexus than in the submucosal plexus (p < 0.05). Moreover, co-treatment of stressed rats with sertraline and nortriptyline could prevent the cellular hyperplasia of the plexuses, with more effective action for sertraline (p < 0.02).

CONCLUSIONS

Stress exposure for 45 days induced hyperplasia of the colon's enteric plexuses in both sexes. However, these drugs could prevent the changes, with a more effective action for sertraline.

摘要

背景

结肠部分受肌间和黏膜下神经丛控制,这些神经丛对压力作出反应,导致一些胃肠道疾病。这些神经丛在肠易激综合征中起作用。患有这种综合征的患者可以用一些抗抑郁药治疗,包括舍曲林和去甲替林。

目的

本研究的主要目的是比较舍曲林和去甲替林对雄性和雌性应激暴露后肠神经元结构变化的影响。次要目的是评估应激对黏膜下和肌间神经丛的影响。

方法

雄性和雌性 Sprague-Dawley 大鼠被分为四组。第一组不接受应激。其他三组接受慢性可变应激(CVS),并给予磷酸盐缓冲液、舍曲林(10mg/kg/天)或去甲替林(10mg/kg/天)。45 天后,使用体视学法估计其结肠神经丛中的神经元数量。

结果

与对照组相比(p<0.002),CVS 组黏膜下神经丛神经元数量增加了 40-51%,肌间神经丛神经元数量增加了 57-69%,但无性别偏好。肌间神经丛的增加明显高于黏膜下神经丛(p<0.05)。此外,应激大鼠同时给予舍曲林和去甲替林治疗可预防神经丛细胞增生,舍曲林的作用更明显(p<0.02)。

结论

45 天的应激暴露导致雌雄两性结肠肠神经丛增生。然而,这些药物可以预防这些变化,舍曲林的作用更明显。

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