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温阳益气汤对洛哌丁胺致便秘模型小鼠的通便作用

Laxative effect of Wenyang Yiqi Decoction on loperamide-induced astriction model mice.

作者信息

Su Yugang, Zhu Renjie, Pang Chunxia, He Zongqi, Wu Bensheng, Wang Xiaopeng

机构信息

Department of Gastroenterology, Changxing Hospital of Traditional Chinese Medicine, Huzhou, China.

Department of Colorectal Surgery, Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.

出版信息

Ann Transl Med. 2023 Feb 28;11(4):170. doi: 10.21037/atm-23-6.

DOI:10.21037/atm-23-6
PMID:36923099
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10009577/
Abstract

BACKGROUND

Although a common disease, astriction is difficult to treat and severely affects quality of life. Wenyang Yiqi Decoction (WYD) is a kind of traditional Chinese medicine (TCM) that is used to treat astriction; however, the mechanism remains unclear. Therefore, this work assessed the laxative effect of WYD on loperamide-induced astriction (LIA) model mice.

METHODS

We replicated a constipation model in mice and detected changes in fecal parameters such as feces quantity and water content, intestinal transit function, and histopathological changes in the constipated mice. After five days of WYD intervention, mouse tissues were taken out for detection. We also measured the levels of gastrin (Gas), substance P (SP), acetylcholinesterase (AChE), and vasoactive intestinal peptide (VIP) in the mice's serum. Additionally, we used quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot to detect c-Kit and stem cell factor (SCF), and examined the effects of WYD on the tight junction (TJ) proteins occludin (Ocln), zonula occludens-1 (ZO-1), and claudin-1 (Cldn-1) in the mice's intestines.

RESULTS

Through histopathological changes, we observed less destruction of epithelial cells and greater integrity of goblet and epithelial cells in WYD-treated mice than in mice in the loperamide group. qRT-PCR and western blot analysis of c-Kit and SCF showed that WYD could boost the levels of c-Kit and SCF. The qRT-PCR and immunohistochemical (IHC) analyses of enteral tight occludin (Ocln), occludenas-1 (ZO-1), and cldin-1 (Cldn-1) showed that WYD could boost the level of ZO-1 and decrease the level of Cldn-1. The study also investigated the effect of WYD treatment on the enteral barrier function of astriction model mice and found that the TJ proteins (ZO-1, Cldn-1) in the colon of the astriction model mice had significant changes compared to the normal group, and WYD intervention was found to increase the expression of ZO-1, and decrease the expression of Cldn-1.

CONCLUSIONS

WYD alleviates LIA by regulating enteral hormones, boosting the number of interstitial cells of Cajal (ICCs), or adjusting enteral block action.

摘要

背景

便秘虽是一种常见疾病,但治疗困难,严重影响生活质量。温阳益气汤(WYD)是一种用于治疗便秘的中药;然而,其作用机制尚不清楚。因此,本研究评估了温阳益气汤对洛哌丁胺诱导的便秘(LIA)模型小鼠的通便作用。

方法

我们在小鼠中复制了便秘模型,并检测了粪便参数的变化,如粪便量和含水量、肠道转运功能以及便秘小鼠的组织病理学变化。温阳益气汤干预五天后,取出小鼠组织进行检测。我们还测量了小鼠血清中胃泌素(Gas)、P物质(SP)、乙酰胆碱酯酶(AChE)和血管活性肠肽(VIP)的水平。此外,我们使用定量实时聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法检测c-Kit和干细胞因子(SCF),并研究温阳益气汤对小鼠肠道紧密连接(TJ)蛋白闭合蛋白(Ocln)、闭合蛋白-1(ZO-1)和紧密连接蛋白-1(Cldn-1)的影响。

结果

通过组织病理学变化,我们观察到与洛哌丁胺组小鼠相比,温阳益气汤治疗组小鼠上皮细胞破坏较少,杯状细胞和上皮细胞完整性更高。对c-Kit和SCF进行qRT-PCR和蛋白质免疫印迹分析表明,温阳益气汤可提高c-Kit和SCF水平。对肠道紧密连接蛋白闭合蛋白(Ocln)、闭合蛋白-1(ZO-1)和紧密连接蛋白-1(Cldn-1)进行qRT-PCR和免疫组织化学(IHC)分析表明,温阳益气汤可提高ZO-1水平并降低Cldn-1水平。该研究还调查了温阳益气汤治疗对便秘模型小鼠肠道屏障功能的影响,发现便秘模型小鼠结肠中的TJ蛋白(ZO-1、Cldn-1)与正常组相比有显著变化,并且发现温阳益气汤干预可增加ZO-1的表达并降低Cldn-1的表达。

结论

温阳益气汤通过调节肠道激素、增加Cajal间质细胞(ICC)数量或调节肠道阻滞作用来缓解洛哌丁胺诱导的便秘。

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