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痛泻要方对结肠上皮分泌Cl和HCO通道的调节作用

Regulating effect of TongXie-YaoFang on colonic epithelial secretion Cl and HCO channel.

作者信息

Yang Cheng, Xiong Ying, Zhang Sheng-Sheng, An Fang-Mei, Sun Jing, Zhang Qing-Lin, Zhan Qiang

机构信息

Cheng Yang, Fang-Mei An, Jing Sun, Qing-Lin Zhang, Qiang Zhan, Department of Gastroenterology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.

出版信息

World J Gastroenterol. 2016 Dec 28;22(48):10584-10591. doi: 10.3748/wjg.v22.i48.10584.

DOI:10.3748/wjg.v22.i48.10584
PMID:28082810
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5192269/
Abstract

AIM: To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula, a Chinese herbal formula, on Diarrhea-predominant irritable bowel syndrome (D-IBS) rats. METHODS: In a neonatal maternal separation plus restraint stress (NMS + RS) model of D-IBS, male Sprague Dawley rats were randomly divided into two groups (NMS + RS group and TXYF-formula group) with no handlings were used as controls (NH group). Starting from postnatal day 60, rats in TXYF-formula group were administered TXYF-formula (4.92 g/100 g bodyweight) orally twice a day for 14 consecutive days while NH group and NMS + RS group were given distilled water. Using short-circuit current technology, we observed 5-HT-induced changes of current across ion channels, such as cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel, epithelial Na channel (ENaC), Ca-dependent Cl channel (CACC), Na-K-2Cl co-transporter (NKCC), and Na-HCO co-transporter (NBC), in the colonic epithelium of three groups after exposure to drugs and specific blockers with a Power Lab System (AD Instruments International). RESULTS: Under basal conditions, the changes of short-circuit current (∆Isc, µA/cm) induced by 5-HT were similar in NH group and TXYF-formula group, and both higher than NMS + RS group (70.86 µA/cm ± 12.32 µA/cm, 67.67 µA/cm ± 11.68 µA/cm 38.8 µA/cm ± 7.25 µA/cm, < 0.01, respectively). When CACC was blocked by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, 5-HT-induced ∆Isc was smaller in NMS + RS group than in NH group and TXYF-formula group, respectively (48.41 µA/cm ± 13.15 µA/cm 74.62 µA/cm ± 10.73 µA/cm, 69.22 µA/cm ± 11.7 µA/cm, < 0.05, respectively). The similar result could be obtained when ENaC was blocked by Amiloride (44.69 µA/cm ± 12.58 µA/cm 62.05 µA/cm ± 11.26 µA/cm, 62.11 µA/cm ± 12.01 µA/cm, < 0.05, respectively). However, when CFTR Cl channel was blocked by 1,1-dimethyl piperidinium chloride (DPC), 5-HT-induced ∆Isc did not significantly differ in three groups (42.28 µA/cm ± 10.61 µA/cm 51.48 µA/cm ± 6.56 µA/cm 47.75 µA/cm ± 7.99 µA/cm, > 0.05, respectively). The similar results could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers. CONCLUSION: TXYF-formula can regulate the Cl and HCO secretion of colonic mucosa CFTR Cl channel, Cl/HCO exchanger, NBC and NKCC co-transporters.

摘要

目的：探讨中药方剂痛泻要方（TXYF）对腹泻型肠易激综合征（D-IBS）大鼠的药理作用。 方法：在D-IBS的新生母鼠分离加束缚应激（NMS + RS）模型中，将雄性Sprague Dawley大鼠随机分为两组（NMS + RS组和TXYF方剂组），未进行任何处理的大鼠作为对照组（NH组）。从出生后第60天开始，TXYF方剂组大鼠每天口服TXYF方剂（4.92 g/100 g体重）两次，连续14天，而NH组和NMS + RS组给予蒸馏水。使用短路电流技术，我们通过Power Lab系统（AD Instruments International）观察了三组大鼠结肠上皮中5-羟色胺（5-HT）诱导的跨离子通道电流变化，如囊性纤维化跨膜传导调节因子（CFTR）氯离子通道、上皮钠离子通道（ENaC）、钙依赖性氯离子通道（CACC）、钠-钾-2-氯共转运体（NKCC）和钠-碳酸氢根共转运体（NBC），在给予药物和特异性阻滞剂后的变化。 结果：在基础条件下，NH组和TXYF方剂组中5-HT诱导的短路电流变化（∆Isc，µA/cm）相似，且均高于NMS + RS组（分别为70.86 µA/cm ± 12.32 µA/cm、67.67 µA/cm ± 11.68 µA/cm和38.8 µA/cm ± 7.25 µA/cm，P < 0.01）。当CACC被4,4'-二异硫氰酸根合芪-2,2'-二磺酸阻断时，NMS + RS组中5-HT诱导的∆Isc分别小于NH组和TXYF方剂组（分别为48.41 µA/cm ± 13.15 µA/cm、74.62 µA/cm ± 10.73 µA/cm和69.22 µA/cm ± 11.7 µA/cm，P < 0.05）。当ENaC被阿米洛利阻断时，也可得到类似结果（分别为44.69 µA/cm ± 12.58 µA/cm、62.05 µA/cm ± 11.26 µA/cm和62.11 µA/cm ± 12.01 µA/cm，P < 0.05）。然而，当CFTR氯离子通道被1,1-二甲基哌啶鎓氯化物（DPC）阻断时，三组中5-HT诱导的∆Isc无显著差异（分别为42.28 µA/cm ± 10.61 µA/cm、51.48 µA/cm ± 6.56 µA/cm和47.75 µA/cm ± 7.99 µA/cm，P > 0.05）。当NBC和NKCC分别被其阻滞剂阻断时，三组中也可得到类似结果。 结论：痛泻要方可调节结肠黏膜的氯离子和碳酸氢根分泌——CFTR氯离子通道、氯/碳酸氢根交换体、NBC和NKCC共转运体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe53/5192269/ad015978305f/WJG-22-10584-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe53/5192269/43fece685410/WJG-22-10584-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe53/5192269/ad015978305f/WJG-22-10584-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe53/5192269/43fece685410/WJG-22-10584-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe53/5192269/ad015978305f/WJG-22-10584-g004.jpg

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本文引用的文献

[1]
The prevalence of coeliac disease in patients fulfilling Rome III criteria for irritable bowel syndrome.

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Inhibitory effect of TongXie-YaoFang formula on colonic contraction in rats.

World J Gastroenterol. 2015-3-14

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