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半夏泻心汤改善洛哌丁胺诱导的功能性消化不良小鼠模型的胃肠功能。

Banha-sasim-tang improves gastrointestinal function in loperamide-induced functional dyspepsia mouse model.

机构信息

Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea.

Department of Herbology, College of Korean Medicine, DaeguHaany University, 136 Shinchendong-ro, Suseong-gu, Daegu, 42158, Republic of Korea.

出版信息

J Ethnopharmacol. 2019 Jun 28;238:111834. doi: 10.1016/j.jep.2019.111834. Epub 2019 Mar 30.

DOI:10.1016/j.jep.2019.111834
PMID:30940567
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Banha-sasim-tang (BST; Hange-shashin-to in Kampo medicine; Banxia xiexin tang in traditional Chinese medicine) is a traditional Chinese harbal medicine that has been commonly used for gastrointestinal disorders.

AIM OF THE STUDY

To investigate the pharmacological effects of BST, a standardized herbal drug, on main symptoms of functional dyspepsia including delayed gastric emptying, and underlying mechanisms of action in mouse model.

METHODS AND MATERIALS

Balb/C mice were pretreated with BST (25, 50, 100 mg/kg, po) or mosapride (3 mg/kg, po) for 3 days, and then treated with loperamide (10 mg/kg, ip) after 19 h fasting. A solution of 0.05% phenol red (500 μL) or 5% charcoal diet (200 μL) was orally administered, followed by scarifying and assessment of gastric emptying or gastro-intestinal motility. C-kit (immunofluorescence), nNOS (western blot) and gastric contraction-related gene expression were examined in stomach tissue.

RESULTS

The loperamide injection substantially delayed gastric emptying, while the BST pretreatment significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of stomach-retained phenol red (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The BST pretreatment significantly tempered the loperamide-induced inactivation of c-kit and nNOS (p < 0.05 or 0.01) as well as the contraction-related gene expression, such as the 5HT receptor (5HTR), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK). The BST pretreatment also significantly attenuated the alterations in gastro-intestinal motility (p < 0.01).

CONCLUSION

Our results are the first evidence of the prokinetic agent effects of Banha-sasim-tang in a loperamide-induced FD animal model. The underlying mechanisms of action may involve the modulation of peristalsis via activation of the interstitial cells of Cajal and the smooth muscle cells in the stomach.

摘要

民族药理学相关性

半夏泻心汤(BST;汉方医学中的半夏泻心汤;传统中药中的半夏泻心汤)是一种常用的治疗胃肠道疾病的中药。

研究目的

研究 BST(一种标准化草药)对功能性消化不良主要症状(包括胃排空延迟)的药理作用及其在小鼠模型中的作用机制。

方法与材料

Balb/C 小鼠用 BST(25、50、100mg/kg,po)或莫沙必利(3mg/kg,po)预处理 3 天,然后禁食 19 小时后用洛哌丁胺(10mg/kg,ip)处理。口服 0.05%苯酚红(500μL)或 5%炭黑饮食(200μL)溶液,然后处死并评估胃排空或胃肠动力。检测胃组织中 c-kit(免疫荧光)、nNOS(western blot)和与胃收缩相关的基因表达。

结果

洛哌丁胺注射显著延迟胃排空,而 BST 预处理显著减轻这种蠕动功能障碍,表现在胃内保留的苯酚红量(p<0.05 或 0.01)和胃重(p<0.05 或 0.01)上。BST 预处理还显著调节了洛哌丁胺引起的 c-kit 和 nNOS(p<0.05 或 0.01)失活以及与收缩相关的基因表达,如 5HT 受体(5HTR)、anoctamin-1(ANO1)、ryanodine 受体 3(RYR3)和平滑肌肌球蛋白轻链激酶(smMLCK)。BST 预处理还显著减轻了胃肠动力的改变(p<0.01)。

结论

我们的结果首次证明了半夏泻心汤在洛哌丁胺诱导的 FD 动物模型中的促动力作用。作用机制可能涉及通过激活胃的 Cajal 间质细胞和平滑肌细胞来调节蠕动。

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