Duan Shaoqi, Imamura Nobuko, Kondo Takashi, Kanda Hirosato, Kogure Yoko, Okugawa Takuya, Fukushima Masashi, Tomita Toshihiko, Oshima Tadayuki, Fukui Hirokazu, Noguchi Koichi, Dai Yi, Miwa Hiroto
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.
J Neurogastroenterol Motil. 2022 Apr 30;28(2):255-264. doi: 10.5056/jnm21204.
BACKGROUND/AIMS: Herbal medicine is an important complementary therapy for functional dyspepsia (FD). However, its effect against gastric hypersensitivity in patients with FD has rarely been evaluated. Yokukansan (YKS), a traditional Japanese herbal medicine, is effective against neuropathic and inflammatory pain. This study aims to use a maternal separation (MS) stress-induced FD model to investigate the effects of YKS against gastric hypersensitivity, gastric motility, and duodenal micro-inflammation.
The MS stress model was established by separating newborn Sprague-Dawley rats from their mothers for 2 hours a day from postnatal days 1 to 10. At the age of 7-8 weeks, the rats were treated with YKS at a dose of 5 mL/kg (1 g/kg) for 7 consecutive days. After YKS treatment, electromyographic activity in the acromiotrapezius muscle by gastric distention and the gastric-emptying rate were assessed. Immunohistochemical analysis of eosinophils in the duodenum and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 in the spinal cord was performed.
YKS treatment suppressed MS stress-induced gastric hypersensitivity and decreased the elevated levels of p-ERK1/2 in the spinal cord. In the gastroduodenal tract, YKS inhibited eosinophil-associated micro-inflammation but did not improve gastric dysmotility.
YKS treatment improved gastric hypersensitivity by alleviating eosinophil-associated micro-inflammation in the gastroduodenal tract. This treatment may be considered an effective therapeutic option for epigastric pain and micro-inflammation in patients with FD.
背景/目的：草药是功能性消化不良（FD）的一种重要补充疗法。然而，其对FD患者胃超敏反应的作用鲜有评估。日本传统草药抑肝散（YKS）对神经性和炎性疼痛有效。本研究旨在利用母婴分离（MS）应激诱导的FD模型，研究YKS对胃超敏反应、胃动力和十二指肠微炎症的影响。
通过在出生后第1天至第10天将新生的Sprague-Dawley大鼠与其母亲每天分离2小时来建立MS应激模型。在7-8周龄时，大鼠连续7天接受剂量为5 mL/kg（1 g/kg）的YKS治疗。YKS治疗后，评估胃扩张时肩峰斜方肌的肌电活动和胃排空率。对十二指肠中的嗜酸性粒细胞和脊髓中的磷酸化细胞外信号调节激酶（p-ERK）1/2进行免疫组织化学分析。
YKS治疗可抑制MS应激诱导的胃超敏反应，并降低脊髓中升高的p-ERK1/2水平。在胃十二指肠中，YKS抑制嗜酸性粒细胞相关的微炎症，但未改善胃动力障碍。
YKS治疗通过减轻胃十二指肠中嗜酸性粒细胞相关的微炎症改善胃超敏反应。这种治疗可能被认为是FD患者上腹部疼痛和微炎症的一种有效治疗选择。
